Emeritus Faculty, Acad Council, Radiation Oncology - Radiation Therapy
Member, Stanford Cancer Institute
Head and neck, interstitial
Bladder, prostate, breast
IORT, stereotactic, pituitary (and brain)
Osteos and other sarcomas, clinical hyperthermia
To determine whether an accelerated course of radiotherapy delivered to the lumpectomy cavity plus margin using IORT as a single dose, intracavitary brachytherapy with the MammoSite device over 5 days, partial breast 3-D CRT in 5 days, or stereotactic APBI over 4 days is a feasible and safe alternative to a six and a half week course of whole breast radiotherapy. The study will measure both short and long-term complications of radiation treatment, short and long-term breast cosmesis, local rates of in-breast cancer recurrence, regional recurrences, distant metastases, and overall survival.
Stanford is currently not accepting patients for this trial. For more information, please contact Sally Bobo, (650) 736 - 1472.
To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.
View details for DOI 10.1016/j.ijrobp.2007.10.027
View details for Web of Science ID 000255971100013
View details for PubMedID 18164839
Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT).Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment.At a median follow-up of 25 months for living patients (range, 10-60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan-Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006).The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients.
View details for DOI 10.1002/hed.20505
View details for Web of Science ID 000244459100002
View details for PubMedID 17111429
Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site.The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy.No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group.Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.
View details for DOI 10.1002/hed.20372
View details for Web of Science ID 000238690100003
View details for PubMedID 16475199
The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC).Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response.The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms.The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.
View details for DOI 10.1002/cncr.21785
View details for Web of Science ID 000237187400010
View details for PubMedID 16532436
Breast-conserving therapy (BCT) is a proven local treatment option for select patients with early-stage breast cancer. This paper reviews pathologic, clinical, and treatment-related features that have been identified as known or potential predictors for ipsilateral breast tumor recurrence in patients treated with BCT. Pathologic risk factors such as the final pathologic margin status of the excised specimen after BCT, the extent of margin involvement, the interaction of margin status with other adverse features, the role of biomarkers, and the presence of an extensive intraductal component or lobular carcinoma in situ all impact the likelihood of ipsilateral breast tumor recurrence. Predictors of positive repeat excision findings after conservative surgery include young age, presence of an extensive intraductal component, and close or positive margins in prior excision. Finally, treatment-related factors predicting ipsilateral breast tumor recurrence include extent of breast radiation therapy, use of a boost to the lumpectomy cavity, use of tamoxifen or chemotherapeutic agents, and timing of systemic therapy with irradiation. The ability to predict for an increased risk of ipsilateral breast tumor recurrence enhances the ability to select optimal local treatment strategies for women considering BCT.
View details for PubMedID 15748463
The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types.The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence.Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%.Further study is needed to determine the optimal surgical management of the N0 and limited N+ neck.
View details for Web of Science ID 000225606400002
View details for PubMedID 15611394
Breast conservation therapy (BCT) is a safe, effective alternative to mastectomy for many women with newly diagnosed breast cancer. This approach involves local excision of the malignancy with tumor-free margins, followed by 5-7 weeks of external beam whole breast (WB) radiotherapy (XRT) to minimize the risk of an in-breast tumor recurrence (IBTR). Though clearly beneficial, the extended course of almost daily postoperative radiotherapy interrupts normal activities and lengthens care. Additional options are now available that shorten the radiotherapy treatment time to 1-5 days (accelerated) and focus an increased dose of radiation on just the breast tissue around the excision cavity (partial breast). Recent trials with accelerated, partial breast irradiation (APBI) have shown promise as a potential replacement to the longer, whole breast treatments for select women with early-stage breast cancer. Current APBI approaches include interstitial brachytherapy, intracavitary (balloon) brachytherapy, and accelerated external beam (3-D conformal) radiotherapy, all of which normally complete treatment over 5 days, while intraoperative radiotherapy (IORT) condenses the entire treatment into a single dose delivered immediately after tumor excision. Each approach has benefits and limitations. This study covers over 2 decades of clinical trials exploring APBI, discusses treatment variables that appear necessary for successful implementation of this new form of radiotherapy, compares and contrasts the various APBI approaches, and summarizes current and planned randomized trials that will shape if and how APBI is introduced into routine clinical care. Some of the more important outcome variables from these trials will be local toxicity, local and regional recurrence, and overall survival. If APBI options are ultimately demonstrated to be as safe and effective as current whole breast radiotherapy approaches, breast conservation may become an even more appealing choice, and the overall impact of treatment may be further reduced for certain women with newly diagnosed breast cancer.
View details for Web of Science ID 000226744200003
View details for PubMedID 15665616
Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.
View details for Web of Science ID 000224353600016
View details for PubMedID 15492173
In a single-institution, double-blind, prospective, randomized trial, we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head-and-neck cancer patients.We randomized 58 head-and-neck cancer patients between oral aloe vera and placebo. To be included in this Phase II protocol, patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002. We examined patients biweekly for mucositis at 15 head-and-neck subsites and administered quality-of-life questionnaires.Patients in the aloe and placebo groups were statistically identical in baseline characteristics. By the end of treatment, the two groups were also statistically identical in maximal grade of toxicity, duration of Grade 2 or worse mucositis, quality-of-life scores, percentage of weight loss, use of pain medications, hydration requirement, oral infections, and prolonged radiation breaks.In our randomized study, oral aloe vera was not a beneficial adjunct to head-and-neck radiotherapy. The mean quality-of-life scores were greater in the aloe vera group, but the differences were not statistically significant. Oral aloe vera did not improve tolerance to head-and-neck radiotherapy, decrease mucositis, reduce soreness, or otherwise improve patient well-being.
View details for DOI 10.1016/j.ijrobp.2004.02.012
View details for Web of Science ID 000223854500022
View details for PubMedID 15337553
Postmastectomy chest wall and nodal radiation therapy decreases local recurrence and improves disease-free and overall survival. Immediate transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after mastectomy has become more common. We report on our experience of irradiating the chest wall and regional lymph nodes after a TRAM flap reconstruction and describe the acute side effects, flap viability, and cosmetic outcome. Between 1995 and 2000, 22 patients with a median age of 47 years (range 27-61 years) received chest wall radiotherapy following mastectomy and immediate pedicled TRAM flap reconstruction. The indication for radiotherapy included tumor size, involved lymph nodes, or positive margins. All patients received chemotherapy before radiotherapy and three patients also received concurrent chemotherapy. The median dose to the chest wall was 50.4 Gy in 28 fractions of 1.8 Gy using a 6 or 4 MV linear accelerator. The patients were all computed tomography (CT) planned in the treatment position. The patients were immobilized using an alpha cradle. Two tangent fields were used to deliver the dose. On alternating days, a customized bolus was applied to the chest wall that spared the central region where the subsequent nipple reconstruction would be performed. All 22 patients completed 90% of the prescribed chest wall radiotherapy dose. Sixty-six percent of the patients received treatment without any treatment breaks. Only 10% of the patients developed desquamation of the TRAM flap skin. Thirty percent developed grade II erythema of the TRAM flap. With median follow-up of 18 months, no TRAM flaps have been lost or required revision. This technique for delivery of radiotherapy to the chest wall in patients who have undergone a mastectomy and immediate TRAM flap reconstruction is well tolerated. The acute toxicity was manageable. There were no TRAM flap losses or revisions performed secondary to the radiotherapy.
View details for PubMedID 15009038
To assess long-term efficacy and toxicity associated with external beam irradiation (EBRT) and interstitial (192)Ir implantation for the treatment of squamous carcinoma of the base of tongue.Between April 1975 and December 1993, 41 patients with base-of-tongue carcinomas were treated with (192)Ir interstitial implants after EBRT at Stanford University. One patient had Stage I, 6 had Stage II, 7 had Stage III, and 27 had Stage IV tumors. Twenty-eight patients had cervical lymph node involvement at diagnosis. All received EBRT to a median dose of 50 Gy (range 48.9-68 Gy) to the primary tumor and regional lymph nodes before brachytherapy. Interstitial implant was performed 2-4 weeks after EBRT. Intraoperatively, nylon catheters were placed via steel trocars into the base of tongue, glossotonsillar groove, and pharyngo-epiglottic fold using a catheter looping technique. Twenty-three of 28 node-positive patients also underwent simultaneous neck dissections. Postoperatively, the (192)Ir seeds were inserted and allowed to remain in place for approximately 35 h to achieve a median tumor dose of 26 Gy (range 20-34 Gy) to a median volume of 73 cc. Survival, local control, and complications were assessed.With a median follow-up of 62 months (range 9-215) for all patients and 90 months for alive patients, the 5-year Kaplan-Meier survival estimate was 66%. The 5-year local control rate was 82%, with 7 patients recurring locally, 2 of whom were salvaged with surgery. Nodal control was achieved in 93% of patients with either EBRT alone or in combination with neck dissection. The 5-year freedom from distant metastasis rate was 83%. Acute complications included transient bleeding (5%) and infection (8%). Late complication included soft-tissue necrosis/ulceration (7%), osteoradionecrosis (5%), and xerostomia.Base-of-tongue carcinoma can be effectively treated with EBRT and (192)Ir implant boost. Local control is excellent and complication rates are acceptable.
View details for DOI 10.1016/S0360-3016(03)00597-2
View details for Web of Science ID 000185315200023
View details for PubMedID 12957261
Plasmablastic lymphoma (PBL), an aggressive non-Hodgkin's lymphoma that carries a poor prognosis, previously has been identified almost exclusively in patients infected with the human immunodeficiency virus (HIV). We present a case of a 42-year-old HIV-negative patient presenting with an isolated nasal cavity mass, the typical presentation for PBL. The patient was given systemic chemotherapy, central nervous system prophylaxis, and consolidative locoregional radiotherapy and achieved a complete clinical response. This case suggests PBL should be considered in HIV-negative patients with characteristic findings.
View details for DOI 10.1007/s00277-003-0684-3
View details for Web of Science ID 000184757100013
View details for PubMedID 12783213
Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.
View details for DOI 10.1016/S0360-3016(03)00117-2
View details for Web of Science ID 000183937500018
View details for PubMedID 12829140
To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas.As part of a larger clinical trial, 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays, performed on fine-needle aspirates at 1 and 2 min after 5 Gy. Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min. Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis, and the distribution of values was quantified using median tail moment (MTM). Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response.There was a significant correlation between the 1- and 2-min MTM (slope = 0.77 +/- 0.03). There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo. No correlation was found between Eppendorf PO2 measurements and comet MTM. There was a statistically significant correlation between the treatment response in the node studied and comet MTMs, whereas no correlation was observed between treatment response and Eppendorf measurements.Comet assays are reproducible, as shown by biopsies at 1 and 2 min. Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia. There was no correlation between Eppendorf PO2 measurements and comet MTM. Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome. Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals.
View details for DOI 10.1016/S0360-3016(02)04503-0
View details for Web of Science ID 000182861500010
View details for PubMedID 12738312
To review the 2- to 17-year outcome of nasopharyngectomy following local recurrence of nasopharyngeal carcinoma.Retrospective review.University medical center.Thirty-seven patients with biopsy-proven recurrent nasopharyngeal cancer followed up for a minimum of 2 years after transpalatal, transmaxillary, and/or transcervical resection with and without neck dissection.Clinical examination, magnetic resonance imaging, chest x-ray examination, and liver function tests to determine re-recurrence; unlimited follow-up.With a mean follow-up of 5.4 years, the crude, 5-year, overall, free-of-disease survival rate was 52%, local control at 5 years was 67%, and the 5-year actuarial survival rate was 60%. Survival by recurrent T stage (rT) was as follows: rT1, 73%; rT2, 40%; rT3, 14%; and rT4, 0%. Complications occurred in 54% and included 1 death from carotid artery injury and 1 patient with permanent pharyngeal plexus paralysis with resultant dysphagia. The remaining patients had transitory complications that spontaneously resolved, required further surgery (closure of palate fistula, debridement, and reapplication of skin graft), or required further medical therapy.The results of this study are better than most published reports of additional irradiation for rT1 and rT2 lesions. More recent radiation studies that use radiosurgery or implants suggest promising early results. A randomized prospective study comparing surgery with additional irradiation for recurrent disease at the primary site is warranted.
View details for Web of Science ID 000174388000013
View details for PubMedID 11886344
To compare computed tomography (CT) with ultrasonography (US) for depiction of the biopsy cavity.Thirty-two consecutive patients who underwent radiation therapy following lumpectomy with a planned electron boost were examined. At the time of simulation for whole-breast radiation therapy, all patients underwent planning CT (CT 1) at 3-mm section intervals. At the time of electron boost simulation, US was performed to define the biopsy cavity. In 17 cases, a second CT examination (CT 2) was performed at the time of electron boost simulation. CT and US studies were reviewed jointly and assigned a cavity visualization score (CVS) of 1 (cavity not visualized) to 5 (all cavity margins clearly defined).The median CVS at CT 1 was 5; at CT 2, 4; and at US, 4. For patients who underwent all three studies, the median CVS at CT 1 was 5; at CT 2, 4; and at US, 4. Factors related to CVS at CT 1 were homogeneous versus heterogeneous appearance (score, 5 vs 4), surgery-to-CT interval (< or =30 days, 5; 31-60 days, 4; >60 days, 4), and cavity size (>15 cm(3), 5; <15 cm(3), 4). In all cases, cavity volume decreased somewhat during the CT 1-to-CT 2 interval.CT performed at the time of whole-breast simulation can be used to plan electron boost fields, with cavity visualization similar to that at US.
View details for Web of Science ID 000167667400029
View details for PubMedID 11274557
A retrospective analysis of the treatment of locally advanced breast cancer (LABC) was undertaken at Stanford Medical Center to assess the outcome of patients who did not undergo surgical removal of their tumors. Between 1981 and 1998, 64 patients with locally advanced breast cancer were treated with induction chemotherapy, radiation with or without breast surgery, and additional chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was followed by local radiotherapy in 59 (92%) patients. Based on the clinical response to chemotherapy and patient preference, 44 (69%) patients received no local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin-containing chemotherapy in all patients. The mean age of patients was 49 years. Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph nodes only). Response to induction chemotherapy was seen in 59 patients (92%), with 29 (45%) achieving a complete clinical response and 30 (47%) a partial clinical response. With a mean follow-up of 51 months (range 7-187 months), 43 patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial 5-year survival is 75%, disease-free survival is 58%, and local control rate is 87.5%. These data indicate that the routine inclusion of breast surgery in a combined modality treatment program for LABC does not appear necessary for the majority of patients who experience a response to induction chemotherapy.
View details for PubMedID 11328324
Three-dimensional treatment planning and CT simulation is widely used for the treatment of a variety of cancers. At the Stanford University Medical Center, a treatment-planning CT scan is obtained before breast irradiation to optimize the dose distribution to the treated breast and to limit radiation to the opposite breast, heart, and lung. In this paper, we review the incidental findings discovered on a careful review of these scans.Between 1997 and 1999, 153 patients referred for breast or chest wall radiation therapy underwent a treatment-planning CT scan in our department. The planning scans were extended to include not only the breast, but also the neck, thorax, and liver. A resident and attending radiation oncologist carefully reviewed each scan before approving the treatment plan. Any abnormal findings were reviewed by an attending in the department of radiology, and additional diagnostic imaging or other evaluation was obtained as necessary.One hundred and fifty-three sequential scans were reviewed, and 17 unsuspected abnormalities were noted (11%). The abnormalities involved the lung (n = 4), the liver (n = 3), the gallbladder (n = 4), the esophagus (n = 2), lymph nodes (n = 3), and the breast. All abnormalities were evaluated with additional imaging studies and/or appropriate consultations. Four of these abnormalities represented additional cancer foci (3%) and altered the treatment plan.Three-dimensional treatment-planning CT scans for breast cancer should be carefully reviewed. In our institution, 11% of these planning studies contained abnormalities, and 3% demonstrated additional unanticipated sites of involvement by breast cancer.
View details for Web of Science ID 000166897800015
View details for PubMedID 11172954
In a study comparing lesbian and heterosexual women's response to newly diagnosed breast cancer, we compared data from 29 lesbians with 246 heterosexual women with breast cancer. Our hypotheses were that lesbian breast cancer patients would report higher scores of mood disturbance; suffer fewer problems with body image and sexual activity; show more expressiveness and cohesiveness and less conflict with their partners; would find social support from their partners and friends; and would have a poorer perception of the medical care system than heterosexual women. Our predictions regarding sexual orientation differences were supported for results regarding body image, social support, and medical care. There were no differences in mood, sexual activity or relational issues. Not predicted were differences in coping, indicating areas of emotional strength and vulnerability among the lesbian sample.
View details for Web of Science ID 000166703200004
View details for PubMedID 11180576
To evaluate the results of different treatment modalities for carcinoma in situ of the glottis, and to identify important prognostic factors for outcome.Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up.Academic tertiary care referral centers.Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days.Initial locoregional control (LRC), ultimate LRC, and larynx preservation.The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3. Of those who failed, the median time to relapse was 11 months for group 1, 17 months for group 2, and 41 months for group 3. Univariate analysis showed that the difference in initial LRC rates between groups 1 and 3 was statistically significant (P =.02), although it was not statistically significant on multivariate analysis (P =.07). Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3.Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients.
View details for Web of Science ID 000165283600001
View details for PubMedID 11074826
A 33-year-old woman with a strong family history of breast cancer who was referred for mammography 5 weeks after completing lactation was found to have new diffuse bilateral microcalcifications in the breast ducts. Contrast material-enhanced magnetic resonance imaging of the breast showed bilateral patchy areas of abnormal enhancement. Large-core needle biopsy showed diffuse calcifications within expanded benign ducts in a background of lactational change, without evidence of malignancy. To the authors' knowledge, these calcifications have not been previously reported and are possibly related to milk stasis or apoptosis associated with lactation.
View details for Web of Science ID 000089452500038
View details for PubMedID 11012452
PURPOSE AND OBJECTIVE: The primary goal of this study was to examine systematically the dosimetric effect of small patient movements and linear accelerator angular setting misalignments in the delivery of intensity modulated radiation therapy. We will also provide a method for estimating dosimetric errors for an arbitrary combination of these uncertainties.Sites in two patients (lumbar-vertebra and nasopharynx) were studied. Optimized intensity modulated radiation therapy treatment plans were computed for each patient using a commercially available inverse planning system (CORVUS, NOMOS Corporation, Sewickley, PA). The plans used nine coplanar beams. For each patient the dose distributions and relevant dosimetric quantities were calculated, including the maximum, minimum, and average doses in targets and sensitive structures. The corresponding dose volumetric information was recalculated by purposely varying the collimator angle or gantry angle of an incident beam while keeping other beams unchanged. Similar calculations were carried out by varying the couch indices in either horizontal or vertical directions. The intensity maps of all the beams were kept the same as those in the optimized plan. The change of a dosimetric quantity, Q, for a combination of collimator and gantry angle misalignments and patient displacements was estimated using Delta=Sigma(DeltaQ/Deltax(i))Deltax(i). Here DeltaQ is the variation of Q due to Deltax(i), which is the change of the i-th variable (collimator angle, gantry angle, or couch indices), and DeltaQ/Deltax(i) is a quantity equivalent to the partial derivative of the dosimetric quantity Q with respect to x(i).While the change in dosimetric quantities was case dependent, it was found that the results were much more sensitive to small changes in the couch indices than to changes in the accelerator angular setting. For instance, in the first example in the paper, a 3-mm movement of the couch in the anterior-posterior direction can cause a 38% decrease in the minimum target dose or a 41% increase in the maximum cord dose, whereas a 5 degrees change in the θ(1)=20 degrees beam only gave rise to a 1.5% decrease in the target minimum or 5.1% in the cord maximum. The effect of systematic positioning uncertainties of the machine settings was more serious than random uncertainties, which tended to smear out the errors in dose distributions.The dose distribution of an intensity modulated radiation therapy (IMRT) plan changes with patient displacement and angular misalignment in a complex way. A method was proposed to estimate dosimetric errors for an arbitrary combination of uncertainties in these quantities. While it is important to eliminate the angular misalignment, it was found that the couch indices (or patient positioning) played a much more important role. Accurate patient set-up and patient immobilization is crucial in order to take advantage fully of the technological advances of IMRT. In practice, a sensitivity check should be useful to foresee potential IMRT treatment complications and a warning should be given if the sensitivity exceeds an empirical value. Quality assurance action levels for a given plan can be established out of the sensitivity calculation.
View details for Web of Science ID 000088159100013
View details for PubMedID 10869760
To explore the feasibility of a multi-modality breast-conserving radiation therapy treatment technique to reduce high dose to the ipsilateral lung and the heart when compared with the conventional treatment technique using two tangential fields.An electron beam with appropriate energy was combined with four intensity modulated photon beams. The direction of the electron beam was chosen to be tilted 10-20 degrees laterally from the anteroposterior direction. Two of the intensity-modulated photon beams had the same gantry angles as the conventional tangential fields, whereas the other two beams were rotated 15-25 degrees toward the anteroposterior directions from the first two photon beams. An iterative algorithm was developed which optimizes the weight of the electron beam as well as the fluence profiles of the photon beams for a given patient. Two breast cancer patients with early-stage breast tumors were planned with the new technique and the results were compared with those from 3D planning using tangential fields as well as 9-field intensity-modulated radiotherapy (IMRT) techniques.The combined electron and IMRT plans showed better dose conformity to the target with significantly reduced dose to the ipsilateral lung and, in the case of the left-breast patient, reduced dose to the heart, than the tangential field plans. In both the right-sided and left-sided breast plans, the dose to other normal structures was similar to that from conventional plans and was much smaller than that from the 9-field IMRT plans. The optimized electron beam provided between 70 to 80% of the prescribed dose at the depth of maximum dose of the electron beam.The combined electron and IMRT technique showed improvement over the conventional treatment technique using tangential fields with reduced dose to the ipsilateral lung and the heart. The customized beam directions of the four IMRT fields also kept the dose to other critical structures to a minimum.
View details for Web of Science ID 000088159100010
View details for PubMedID 10869757
To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease.Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed.The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero.The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.
View details for Web of Science ID 000085401800008
View details for PubMedID 10673517
To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma.We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months.The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse.The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.
View details for Web of Science ID 000085412400004
View details for PubMedID 10701732
This study was conducted to assess the effectiveness of the 1997 American Joint Committee on Cancer (AJCC) staging system to predict survival and local control of patients with maxillary sinus carcinoma and to identify significant factors for overall survival, local control, and distant metastases in patients with these tumors.Ninety-seven patients with maxillary sinus carcinoma were treated with radiotherapy at Stanford University and the University of California, San Francisco between 1959-1996. The histologic type of carcinoma among the 97 patients were: 58 squamous cell carcinomas, 4 adenocarcinomas, 16 undifferentiated carcinomas, and 19 adenoid cystic carcinomas. All patients were restaged clinically according to the 1977 and 1997 AJCC staging systems. The T classification of the tumors of the patients was as follows: 8 with T2, 18 with T3, and 71 with T4 according to the 1977 system and 8 with T2, 36 with T3, and 53 with T4 according to the 1997 system. Eleven patients had lymph node involvement at diagnosis. Thirty-six patients were treated with radiotherapy alone and 61 received a combination of surgical and radiation treatments. The median follow-up for surviving patients was 78 months.The 5-year and 10-year actuarial survival rates for all patients were 34% and 31%, respectively. The 5-year survival estimate by the 1977 AJCC system (P = 0.06) was 75% for Stage II, 19% for Stage III, and 34% for Stage IV and by the 1997 AJCC system (P = 0.006) was 75% for Stage II, 37% for Stage III, and 28% for Stage IV. Significant prognostic factors for survival by multivariate analysis included age (favoring younger age, P<0.001), 1997 T classification (favoring T2-3, P = 0. 001), lymph node involvement at diagnosis (favoring N0, P = 0.002), treatment modality of the primary tumor site (favoring surgery and radiotherapy, P = 0.009), and gender (favoring female patients, P = 0.04). The overall radiation time was of borderline significance (favoring shorter time, P = 0.06). The actuarial 5-year local control rate was 43%. By the 1977 AJCC system (P = 0.78) it was 62% with T2, 36% with T3, and 45% with T4 and using the 1997 AJCC system (P = 0.29) it was 62% with T2, 53% with T3, and 36% with T4. The only significant prognostic factor for local control for all patients by multivariate analysis was local therapy, favoring surgery and radiotherapy over radiotherapy alone (P< 0.001). For patients treated with surgery, pathologic margin status correlated with local control (P = 0.007) and for patients treated with radiation alone, higher tumor dose (P = 0.007) and shorter overall treatment time (P = 0.04) were associated with fewer local recurrences. The 5-year estimate of freedom from distant metastases was 66%. The 1997 T classification, N classification, and lymph node recurrence were adverse prognostic factors for distant metastases on multivariate analysis. There were 22 complications in 16 patients, representing a 30% actuarial risk of developing late complications at 10 years.The 1997 AJCC staging system was found to be superior to the 1977 AJCC staging system in predicting both survival and local control in this patient population. Combined surgical and radiation treatment to the primary tumor yielded higher survival and local control than radiotherapy alone. Other significant prognostic factors for survival were patient age, gender, and lymph node (N) classification. Prolonged overall radiation time was associated with poorer survival and local control. Late severe toxicity from the treatment of these tumors was a significant problem in long term survivors. Improved radiotherapy techniques should lead to decreased injury to the surrounding normal tissues. (c) 1999 American Cancer Society.
View details for Web of Science ID 000083430700011
View details for PubMedID 10547542
Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma.Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy).All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases.Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.
View details for Web of Science ID 000083624000013
View details for PubMedID 10571198
(1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors.Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years).The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted.Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.
View details for Web of Science ID 000082784400010
View details for PubMedID 10577702
Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.
View details for Web of Science ID 000087727900012
View details for PubMedID 10853100
To examine the dosimetric axillary nodal coverage with standard tangential breast radiation fields and determine the utility of three-dimensional treatment planning for such coverage.Six consecutive patients who were to undergo whole-breast irradiation underwent computed tomographic scanning with 5-mm sections at the time of treatment simulation. Contours were made with a commercial workstation for the lower axillary tissues, lungs, and heart. Axillary coverage was examined with three-dimensional isodose visualization and dose-volume histograms for four plans for each patient: (a) standard tangential radiation fields designed to cover only the breast, with clinical setup; (b) standard tangential fields with beam's-eye-view optimization of collimator angles for axillary and breast coverage; (c) standard tangential fields with adjustment of field width and collimator angles; and (d) customized fields, by adjusting width, collimator angle, and gantry angle and by using customized blocks.With plan a, only one patient had a simulated mean axillary dose greater than 90% of that prescribed. Underdosing occurred primarily in the posterior-superior axillary nodal region. Plan b improved axillary coverage; five patients had a simulated mean axillary dose of 89% or more of the prescribed dose, with adequate whole-breast coverage and no increased pulmonary or cardiac doses. Adjusting the field width and gantry angle further improved simulated mean axillary doses; however, customized blocking was then required to avoid increased mean pulmonary and cardiac doses and unacceptable contralateral breast doses.When coverage of lower axillary nodal tissue is desired at breast irradiation, three-dimensional planning with beam's-eye-view adjustment of tangential fields should be considered.
View details for Web of Science ID 000077692800041
View details for PubMedID 9885612
To investigate clinicopathologic predictive criteria for the optimal management of neck metastases in patients with advanced head and neck cancers treated with combined chemoradiotherapy.Prospective study, 48 patients. Mean length follow-up, 23 months.Neck stage predicted neck response to chemoradiotherapy; N3 necks showed more partial responses (P = 0.04), and N1 necks showed more complete responses (P = 0.12). Primary tumor site strongly predicted the pathologic response found on neck dissection in patients with a clinical partial response (cPR) following chemoradiotherapy. There was no difference in survival between patients with a clinical complete response (cCR) after chemoradiotherapy, and patients with a pathologic complete response (pCR) after neck dissection (P = 0.20); however, when grouped together, these patients survived longer than did patients with a pPR at neck dissection (P = 0.06).Clinical response to induction chemotherapy is a poor predictor of ultimate neck control. Induction chemotherapy followed by chemoradiotherapy, and planned neck dissection for patients with persistent cervical lymphadenopathy, provides good regional control.
View details for Web of Science ID 000077441400013
View details for PubMedID 9874431
Although concomitant radiation therapy (RT) and bolus 5-Fluorouracil (5-FU) have been shown to improve survival in locally confined pancreatic cancer, most patients will eventually succumb to their disease. Since 1994, we have attempted to improve efficacy by administering 5-FU as a protracted venous infusion (PVI). This study compares treatment intensity and acute toxicity of consecutive protocols of concurrent RT and 5-FU by bolus injection or PVI.Since 1986, 74 patients with resected or locally advanced pancreatic cancer were treated with continuous course RT and concurrent 5-FU by bolus injection (n = 44) or PVI throughout the course of RT (n = 30). Dose intensity was assessed for both 5-FU and radiotherapy. Toxicity endpoints which could be reliably and objectively quantified (e.g., neutropenia, weight loss, treatment interruption) were evaluated.Cumulative 5-FU dose (mean = 7.2 vs. 2.5 gm/m2, p < 0.001) and weekly 5-FU dose (mean = 1.3 vs. 0.5 gm/m2/wk, p < 0.001) were significantly higher for patients receiving PVI 5-FU. Following pancreaticoduodenectomy, 95% of PVI patients maintained a RT dose intensity of > or = 900 cGy/wk, compared with 63% of those receiving bolus 5-FU (p = 0.02). No difference was seen for patients with locally advanced disease (72% vs. 76%, p = n.s.). Grade II-III neutropenia was less common for patients treated with PVI (13% vs. 34%, p = 0.05). Grade II-III thrombocytopenia was uncommon (< or = 3%) in both treatment groups. Mean percent weight loss (3.8% vs. 4.1%, p = n.s.) and weight loss > or = 5% of pre-treatment weight (21% vs. 31%, p = n.s.) were similar for PVI and bolus treatment groups, respectively. Treatment interruptions for hematologic, gastrointestinal or other acute toxicities were less common for patients receiving PVI 5-FU (10% vs. 25%, p = 0.11).Concurrent RT and 5-FU by PVI was well tolerated and permitted greater chemotherapy and radiotherapy dose intensity with reduced hematologic toxicity and fewer treatment interruptions compared with RT and bolus 5-FU. Longer follow-up will be needed to assess late effects and the impact on overall survival.
View details for Web of Science ID 000071164200015
View details for PubMedID 9422563
Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated.Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction.All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49).Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.
View details for Web of Science ID A1997XB01200004
View details for PubMedID 9169805
The use of chemotherapy and irradiation for organ preservation attempts to eliminate the need for extensive surgery in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). We sought to characterize the morbidity of surgery in patients who needed surgery after treatment with induction chemotherapy followed by simultaneous chemotherapy and radiotherapy (chemoradiotherapy). The surgical morbidity within the first 30 postoperative days of 17 patients treated in an organ preservation approach between July 1991 and December 1994 was compared with a control group of patients undergoing similar surgical procedures during the same period. The organ preservation study patients underwent surgical procedures consisting of 18 neck dissections and 5 resections of the primary site. Six patients in the organ preservation study group experienced 8 surgical complications within the first 30 postoperative days, and most complications were minor. There was no significant difference in the duration of surgery or length of hospitalization between study patients and matched controls. Our surgical complication rate (35.3%) was higher but not statistically different from that of the control group, and compared favorably to reports of surgical morbidity (44% to 61%) in the literature on patients treated with chemoradiotherapy. The lower complication rate seen in this study may be a reflection of early surgical intervention as part of our organ preservation study scheme, the preponderance of neck dissections performed, and the limited number of pharyngeal procedures performed.
View details for Web of Science ID A1997WH40500005
View details for PubMedID 9041815
Advanced laryngeal cancers frequently require total laryngectomy (TL). Some of these cancers, however, are suitable for near-total laryngectomy (NTL). We review our experience with NTL over a 14-year period and compare the functional results with those obtained over the same period using TL followed by tracheoesophageal puncture (TEP). One particular interest was the results achieved when surgery was preceded or followed by radiation therapy. From January 1980 through December 1994, 22 patients underwent NTL. The mean age of the 19 men (86.4%) and 3 women (13.6%) was 61.1 +/- 9.9 years. Follow-up ranged from 4 to 109 months, with a mean of 26.5 months. The local control rate was 90.9% (i.e., 20 of the 22 patients). Over the same time period, 11 TEPs were performed in 7 men (63.6%) and 4 women (36.4%) who had a mean age of 60.4 +/- 7.2 years. Compared with the TEP group, the patients in the NTL group had higher mean scores for swallowing, aspiration, and voice quality evaluations, although the differences were not statistically significant. Notably, 21 of 22 patients (95.5%) received preoperative or postoperative radiotherapy. Complications in the NTL group included aspiration, dilated shunt appendix, and inadequate tracheopharyngeal shunt function. Slight modifications of the NTL technique, including routine entrance into the vallecula in uninvolved larynges, the use of contralateral pyriform mucosa flaps, and the performance of an H-flap tracheostomy are described. The NTL is a sound oncologic procedure for tumors causing vocal cord fixation, and it can be successful even when postoperative radiotherapy is administered. The quality of speech, the ease of swallowing, and the incidence of aspiration are similar to those in patients who have had a TEP following TL.
View details for Web of Science ID A1996VG63300019
View details for PubMedID 8822722
The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear.The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years.The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors.The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.
View details for Web of Science ID A1995RH15100015
View details for PubMedID 8625101
Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study.From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures.Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively.From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.
View details for Web of Science ID A1994MP35300020
View details for PubMedID 8270436
To describe the long-term results of radiotherapy as treatment for carcinoma-in-situ of the glottic larynx.Twenty-nine patients with a histologic diagnosis of carcinoma-in-situ (CIS) of the true vocal cord were treated in the Department of Radiation Oncology at Stanford University Medical Center over a 32-year period from 1958-1990. Twenty patients were treated at the time of initial diagnosis following biopsy only (12) or vocal cord stripping (8) and the remainder were referred for treatment of recurrent CIS following one or more prior surgical procedures. Treatment was delivered with megavoltage equipment to a total dose of 53-66.5 Gy (mean 62 Gy) in 180-250 cGy fractions. The mean follow-up time is 10 years, with a range of 2-27 years.Two patients relapsed locally. One patient had recurrent CIS 5 months after radiotherapy and was salvaged with vocal cord stripping. The other developed microinvasive squamous cell carcinoma and underwent total laryngectomy. The actuarial freedom from local relapse and overall survival at 10 years are 92% and 64%, respectively. No local failures occurred more than 5 years after treatment. Late complications from radiotherapy were rare, and voice quality was good-to-excellent in 90% of patients. The actuarial risk of a second aerodigestive tract malignancy is 11% at 10 years.Radiation therapy is an effective and safe treatment modality for carcinoma-in-situ of the glottic larynx. Long-term local control is achieved in approximately 90% of patients with 75% having normal voice.
View details for Web of Science ID A1994MP35300031
View details for PubMedID 8270448
To evaluate the results, techniques, indications and complications of interstitial brachytherapy in the management of squamous cell carcinomas of the tonsil and soft palate, we reviewed the Stanford University Medical School experience with this modality.Between May 1975 and January 1990, 37 patients with squamous cell carcinomas of the Tonsillo-Palatine region were treated with a combination of external beam irradiation and a removable Iridium-192 interstitial implant. The mean age of these patients was 56. Twenty-two were males and 15 were females. The stage distribution included four patients with Stage I, 5 with Stage II, 10 with Stage III, and 18 with Stage IV cancers. Thirty-two percent (12/37) of these patients had T3 or T4 lesions. Forty-nine percent (18/37) had stage N2 or N3 cervical lymphadenopathy. All 37 patients received initial external beam irradiation to the primary, bilateral necks, and supraclavicular region (mean dose: 5400 cGy, range 4000-6600). Eighteen patients (49%) also received neck dissections. All 37 patients received an interstitial Irridium-192 implant using a combination intraoral swage and external looping technique. The mean dose was 2700 cGy (range 2000-4000 cGy) to an average volume of 24 cc (range 5-81).Local control was obtained in 95% (35/37) of the patients. Eighty-seven percent (32/37) of the patients have remained disease-free in the neck. Nine patients have developed second primary lesions, and one developed pulmonary metastasis. Fifteen patients have died (6 succumbed to their cancers, 6 to second primaries, 2 to intercurrent disease, 1 from an unknown cause). The actuarial freedom from relapse is 75%, and overall survival is 64% at 5 years, with a mean follow up of 43 months (range 5-110). Complications were limited to one case of osteoradionecrosis of the mandible and one tonsillar ulcer. Functional and esthetic integrity was preserved in most of these patients.Iridium-192 interstitial implant boost combined with external beam radiation therapy is a safe and effective therapy in the management of locally advanced carcinomas of the tonsil and soft palate.
View details for Web of Science ID A1994MP35300028
View details for PubMedID 8270445
Brachytherapy is a useful addition to external beam irradiation in the treatment of patients with head and neck cancer. Removeable implants are especially important in the treatment of neoplasms of the oral cavity (tongue, floor of mouth, buccal mucosa), orophrynx (tonsil, palate, and base tongue) and nasopharynx (intracavitary boosts). The most commonly used isotope for removable implants is irdium 192. The remote afterloading technique is applicable to both interstitial and intracavitary removable implants. Permanent placement of iodine 125 and palladium 103 radioactive sources may be performed for recurrent nasophayngeal malignancies, for palliation of accessible recurrences of primary sites in the oral cavity, oropharynx, and hypopharynx, or for cervical lymph node metastases. With brachytherapy, high radiation doses may be delivered to the volume of interest, while at the same time protecting adjacent normal tissues. Such implantations, if carefully performed, are effective, safe, and have a low risk of complications.
View details for PubMedID 10717077
Seven patients received stereotaxic radiosurgery for 10 lesions at the base of the skull (BOS) from recurrent head and neck malignant neoplasms.A radiation dose of 17.5-35.0 Gy was delivered as a single fraction. Follow-up ranged from 1 to 14 months.Nine lesions were symptomatic, and the symptoms improved in five and stabilized in four lesions. In addition, a significant radiographic response was observed in 4 of 10 recurrences. Cranial nerve signs developed in two patients, and an area of asymptomatic necrosis developed in one patient in the temporal lobe tip.From their brief experience, the authors conclude that stereotaxic radiosurgery may be a promising treatment in locally controlling recurrent head and neck cancers that involve the BOS.
View details for Web of Science ID A1992JP69200027
View details for PubMedID 1525775
Results are reported of transpalatal, transcervical, and transmaxillary resection in 15 patients with recurrent nasopharyngeal cancer after failure of primary radiotherapy. Seven patients treated for cure have been followed up for more than 3 years (mean, 55 months; range, 40 to 82 months), with three (43%) remaining free of disease. Two patients are living with local disease (59 and 40 months postoperatively), while two have died of their local and regional recurrence (40 and 17 months postoperatively). Two additional patients underwent nasopharyngectomy for palliation. One of these patients died of uncontrolled disease 12 months postoperatively; the other remains alive with disease 70 months after resection. Six patients have been followed up for less than 3 years (mean, 22.3 months; range, 16 to 32 months). Of this group, one (17%) is without evidence of disease, four are living with local disease (13, 16, 17, and 27 months postoperatively), and one has died of disease (13 months postoperatively). Recurrence (10 of 13 patients) has occurred an average of 8 months after surgery (range, 4 to 17 months). Complications include transient marginal mandibular nerve weakness (one), permanent cranial nerve paralysis (two), nasopharyngitis and/or osteomyelitis of the cervical vertebrae or base of skull requiring intravenous antibiotics (two), aspiration pneumonia (two), prolonged nasogastric tube feeding (two), and intraoperative thyroid storm (one). No cerbrospinal fluid leaks or perioperative deaths occurred. The long-term cure rate and disease-free interval of transpalatal nasopharyngectomy lead us to believe that this technique is probably only slightly better than reirradiation in the appropriately selected patient.
View details for Web of Science ID A1991GN85300006
View details for PubMedID 1747224
From 1956 to 1988, 57 children and young adults (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at The University of Texas M.D. Anderson Cancer Center (42 patients) and Stanford University Medical Center (15 patients). The male to female ratio was 2:1. Forty-three patients had lymphoepithelioma, seven had undifferentiated neoplasms, and seven had squamous cell carcinoma. Two patients had Stage III disease and the remainder had Stage IV disease at the time of presentation. All patients were treated with primary radiotherapy, and 14 patients also had chemotherapy with combinations of the following drugs: dactinomycin, doxorubicin, bleomycin, cisplatin, cyclophosphamide, fluorouracil, methotrexate, and vincristine. Twenty-six patients are alive 6 to 178 months from the first day of treatment (median 93 months). The 5- and 10-year actuarial survival rates are 51% and 36%, respectively, and the corresponding disease specific survival rates were 51% and 51%. There were no recurrences after 42 months. The patterns of failure were as follows: distant metastasis only, 21 patients; locoregional metastasis only, 1; both, 5. Distant metastases most commonly occurred in bones, lungs, liver, and mediastinal lymph nodes. Chronic treatment-related morbidity was encountered in a significant number of long term survivors. Trends in the data not reaching statistical significance suggest a more favorable prognosis for a) females, b) patients less than or equal to 15 years of age, c) lymphoepithelioma or undifferentiated histologies, d) stages T3-4 NO-1 vs T1-2 N2-3 vs T3-4 N2-3, e) primary tumor dose greater than or equal to 65 Gy and f) patients who received chemotherapy.
View details for Web of Science ID A1990EE63800007
View details for PubMedID 2120164
Adenoid cystic carcinomas (ACC) of the salivary glands are aggressive tumors characterized by multiple late local recurrences and distant metastases. Current therapy includes wide local excision and high-dose postoperative radiation therapy (XRT) (5400 to 7000 cGy). Despite early aggressive treatment, local recurrence remains a major problem with limited safe and effective therapeutic options available. The excellent local responses obtained in four patients (six sites) with ACC of the head and neck treated either with additional low-dose irradiation (2160 to 3420 cGy) in conjunction with two to five hyperthermia (HT) treatments or with full dose XRT and HT as part of the overall treatment plan are reported. All HT treatments were for 45 minutes once steady state conditions were obtained. Monitored intratumoral temperatures for all treatments achieved average maximum (Tmax), average mean (Tave), and average minimum (Tmin) temperatures of 44.2 degrees C, 41.2 degrees C, and 38.9 degrees C, respectively. A complete response was obtained for all six fields with no significant long-term complications. Two patients remain alive and free of local disease at 42 and 63 months of follow-up. Two patients died--one with metastases (with persistent local control) and one with a local recurrence at 9 and 30 months, respectively, after XRT and HT. This is the first report of HT and low-dose XRT in the management of previously irradiated ACC and suggests a potential role for the use of this modality in the treatment of ACC.
View details for Web of Science ID A1990DH06600008
View details for PubMedID 2160315
Since September 1983, five patients with head and neck cancers and five patients with pelvic or perineal recurrences of colorectal neoplasms received 192Ir interstitial implants through flexible afterloading catheters that were modified to allow RF hyperthermia treatments of the tumor within 1 hr pre- and post-brachytherapy. Local control in the implant volume was obtained in three of the patients with head and neck cancers (base tongue--2/4; floor of mouth--1/1) with follow-up of 9 to 42 months. Two patients had local recurrences after disease-free periods of 8 and 24 months. Two of the five patients treated for pelvic recurrences had complete responses lasting less than 3 months; prolonged stabilization (12 months) of a presacral mass in a third patient also occurred, but the neoplasm eventually regrew. Average temperatures of 39.2 degrees C to 43.7 degrees C were obtained in the implant volumes of these patients during the 45 minute heating periods which took place prior to loading, and just after removal, of the 192Ir seeds in each patient. No instances of intra or post-operative hemorrhage or necrosis of bone or soft tissues occurred in these patients. However, one individual required a permanent tracheostomy for persistent epiglottic edema after implantation as part of a base-tongue brachytherapy procedure. Interstitial RF hyperthermia in conjunction with brachytherapy appears to be a relatively safe and effective modality, but must be tested prospectively to compare its efficacy to interstitial irradiation alone.
View details for Web of Science ID A1990CK39500026
View details for PubMedID 2298623
Head and neck squamous cancers are a heterogeneous group of neoplasms with varying etiologic factors, presenting symptoms, staging, treatment, and expected outcome. In this monograph, we discuss principles of management common to all sites as well as individual differences. The presenting symptoms of disease are reviewed, stressing the importance of early diagnosis. Accurate pathologic diagnosis can be improved on in difficult cases by newer immunohistochemical techniques. Following diagnosis, accurate clinical staging must be performed, and the evaluation of an unknown primary in the neck is described. We review general considerations for planning the treatment of head and neck cancer, and then discuss specific guidelines for individual sites, stressing the optimal integration of surgery and radiation therapy, particularly brachytherapy. Controversial management issues and new, innovative approaches are discussed. The conventional use of chemotherapy in head and neck cancer is for palliation of recurrent disease. In recent years, chemotherapy has been added to the primary treatment program in an induction role, as a radiosensitizer, as an adjunct following standard therapy, and for organ preservation. The current status of these roles is reviewed. This is a cancer for which there are known etiologic agents. Future efforts in this disease should be directed toward early detection and prevention.
View details for PubMedID 2194750
Nine patients have undergone transpalatal resection of recurrent nasopharynx cancer 10 to 56 months following a full course of external beam irradiation. Seven patients were treated for cure, and two were treated palliatively because of nasal airway obstruction, recurrent epistaxis, and severe headaches. Of the patients treated for cure, five are living free of disease 6 to 48 months (mean, 22.2 months) after their surgery. Disease recurred in two patients at 5 and 7 months. Both underwent secondary procedures and are alive with disease at 25 months and 11 months, respectively. The mean hospital stay was 8.7 days (range, 2 to 30 days) for all patients. The average time to swallowing was 2 days (range, 1 to 3 days). Six patients required resection of their soft palate and a soft palate obturator; two patients had intact functioning soft palates without velopharyngeal insufficiency. Of the two patients treated for palliation, one patient died 1 year postoperatively and, although she received some benefit from the resection (diminished headaches), in retrospect, surgery was not worthwhile. The second patient is alive 3 years following her resection and remained symptom-free for 2 years.
View details for Web of Science ID A1988Q795600013
View details for PubMedID 2460711
Endobronchial brachytherapy is being used with increased frequency in the treatment of recurrent neoplastic obstruction of the major airways, alone or in combination with Nd-YAG laser ablation of the occluding tumor mass. Currently available catheter systems are not reliable with respect to accurate and simple bronchoscopic guidance during placement. Flexibility, wall strength and radiation transmission characteristics are not optimized. We describe a system that meets these goals which has been designed and tested in our department. It is composed of an external handle, deflecting guidewire, and catheter specially modified for endobronchial brachytherapy, with a tip that can be maneuvered in any direction with one hand from outside the patient. Major advantages of the system are ease of concurrent bronchoscopy and catheter guidance, good dosimetric characteristics of the catheter, reasonable cost, and ready availability for adaptation to various techniques of endobronchial brachytherapy.
View details for Web of Science ID A1988P791200028
View details for PubMedID 3403325