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Background: Achieving locoregional control in high-risk patients with head and neck cancer who are poor candidates for standard continuous-course (chemo) radiotherapy due to advanced age, comorbidities, or very advanced disease is challenging. At our Institution, we have significant experience with a regimen of split-course, accelerated, hypofractionated radiotherapy (SCAHRT) for these patients., Patients and Methods: The SCAHRT regimen consisted of 60-72 Gy in 20-24 fractions separated by several weeks mid-course to allow for toxicity recovery and disease reassessment. It was used for patients with advanced age, significant co-morbidities, anticipated intolerance to definitive (chemo)radiation, and those with oligometastatic disease. Disease-free and overall survival rates were calculated using Kaplan-Meier analysis., Results: Fifty-eight out of 65 patients (89%) completed both courses of treatment. Patients without metastatic or recurrent disease were evaluated for treatment response and survival (n=39). Among this group, total tumor response was 91%, and median locoregional failure-free survival and overall survival were 25.7 and 8.9 months, respectively., Conclusion: In high-risk patients unable to tolerate continuous-course definitive (chemo)radiation, SCAHRT is a safe, well-tolerated and effective method of achieving durable locoregional disease control. In properly selected patients, this regimen is preferable to purely palliative approaches., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens., Methods: Patients with locally advanced HNSCC were treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100 mg/m(2) on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m(2) /day) and 5-fluorouracil (5-FU; 1000 mg/m(2) /day) continuous 96-hour infusions on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS)., Results: Between February 2008 and October 2011, 69 patients were enrolled in this study. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. Eighty-three percent of patients had oropharyngeal cancer, of these, 86% were human papillomavirus (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41 months) for arms A and B were: RFS 87% versus 80% (p = .24), overall survival 97% versus 85% (p = .013), locoregional control 96% versus 94% (p = .52), and distant metastatic control 91% versus 87% (p = .9)., Conclusion: Multiagent was not superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes., (© 2014 Wiley Periodicals, Inc.)

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m(2) /day) and cisplatin (20 mg/m(2) /day) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer., (© 2014 International Society for Diseases of the Esophagus.)

Objectives: Long term swallowing dysfunction in patients with oropharynx squamous cell carcinoma (OPSCC) treated with concurrent chemoradiation (CRT) is declining. While the use of intensity modulated radiotherapy (IMRT) is commonly believed to be a potential cause, we hypothesize that the increasing incidence of human papillomavirus (HPV) related disease may also favorably impact this outcome., Materials and Methods: We reviewed 130 HPV+ and 17 HPV- patients with stage III-IV OPSCC treated exclusively with conventional 3-field radiotherapy with chemotherapy between 2002 and 2010. The rates of normal diet, limited diet (significant restrictions in the types of foods eaten, and/or requiring nutritional supplementation for weight maintenance) and feeding tube dependence (FTD) were compared between HPV+ and HPV- patients. Cox proportional hazards modeling were used to perform univariate analysis (UVA) to examine predictors of a combined endpoint of dietary limitation, which included limited diet and/or FTD. These outcomes were also compared to our previously reported cohort of OPSCC patients treated between 1989 and 2002 to assess changes in toxicity over time given the changing disease epidemiology, in the setting of identical treatment regimens., Results: With a median follow-up of 55 months, HPV+ patients more frequently had resumed a normal diet (87% vs. 65%) at last follow up and had lower rates of limited diet (9% vs. 18%) and FTD (4% vs. 18%) compared to HPV- patients (p=0.02). HPV status was the only significant predictor of reduced swallowing dysfunction on UVA (HR 0.19; p=0.008). When compared to our 1989-2002 cohort, patients treated between 2002 and 2010 had less FTD (7.5% vs. 34%, p<0.001) and dietary limitations (26% vs.46%, p<0.001) at 6 months post treatment., Conclusions: HPV+ patients with OPSCC have reduced late swallowing dysfunction after chemoradiation compared to HPV- patients. The changing epidemiology of OPSCC may play a role in toxicity reduction in these patients, independent of the increasing use of IMRT., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy., Methods: Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy., Results: Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control., Conclusions: Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.

Background: Tumor human papillomavirus (HPV) status has emerged as one of the most powerful prognostic factors for disease control and survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). We reviewed our experience in patients with OPSCC and known tumor HPV status treated with definitive chemoradiotherapy (CRT)., Methods: Patients with stage III-IVb OPSCC and known tumor HPV status treated with CRT between 2006 and 2011 were identified from an IRB approved registry for this retrospective review. Outcomes were estimated using the Kaplan-Meier method and compared between HPV-positive and negative patients using the log-rank test., Results: Of the 121 pts (89% male, 93% Caucasian) included in this study, median age was 57 (range: 40-73) and median follow-up was 21 months (range: 6-63). Ninety-seven (80%) patients were HPV-positive and 24 (20%) were HPV-negative. Primary site was base of tongue (55%), tonsil (44%), and oropharyngeal wall (2%). Two year rates of locoregional recurrence (3% vs. 26%; p = 0.002), disease free survival (93% vs. 64%; p = 0.001) and overall survival (94% vs 73%; p = 0.002) were superior in HPV-positive patients, while rates of distant recurrence were similar (3% vs. 5%; p = 0.98). While acute toxicities were similar between both groups, patients with HPV-positive disease were more likely to resume a normal diet (90% vs. 65%; p = 0.017) at last follow up. Also, no HPV-positive patient required a feeding tube beyond 6 months after treatment, compared with 24% of HPV-negative patients., Conclusions: Definitive CRT produces excellent rates of disease control with minimal late toxicity for patients with HPV-positive OPSCC. Studies of OPSCC should account for tumor HPV status when identifying factors prognostic for outcome.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated., (© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Purpose: To report our 20 yr experience of definitive radiotherapy for early glottic squamous cell carcinoma (SCC)., Methods and Materials: Radiation records of 141 patients were retrospectively evaluated for patient, tumor, and treatment characteristics. Cox proportional hazard models were used to perform univariate (UVA) and multivariate analyses (MVA). Cause specific survival (CSS) and overall survival (OS) were plotted using cumulative incidence and Kaplan-Meir curves, respectively., Results: Of the 91% patients that presented with impaired voice, 73% noted significant improvement. Chronic laryngeal edema and dysphagia were noted in 18% and 7%, respectively. The five year LC was 94% (T1a), 83% (T1b), 87% (T2a), 65% (T2b); the ten year LC was 89% (T1a), 83% (T1b), 87% (T2a), and 53% (T2b). The cumulative incidence of death due to larynx cancer at 10 yrs was 5.5%, respectively. On MVA, T-stage, heavy alcohol consumption during treatment, and used of weighted fields were predictive for poor outcome (p < 0.05). The five year CSS and OS was 95.9% and 76.8%, respectively., Conclusions: Definitive radiotherapy provides excellent LC and CSS for early glottis carcinoma, with excellent voice preservation and minimal long term toxicity. Alternative management strategies should be pursued for T2b glottis carcinomas.

Background: This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC)., Methods: Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib., Results: Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts., Conclusions: Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: The reported decreasing benefit with increasing age from concurrent chemoradiotherapy in head and neck cancer patients prompted this retrospective review., Methods: Two courses of cisplatin-based concurrent chemoradiotherapy were given to fit patients ≥70 years with locoregionally advanced cancers. Clinical characteristics, treatment, and outcomes were compared with those for an identically treated cohort <70 years., Results: There were 44 patients ≥70 and 137 patients <70 years. Clinical characteristics, treatment and toxicities were similar except that the elderly were less likely to receive both chemotherapy courses, experienced more myelosuppression, required more unplanned hospitalization, and were feeding-tube dependent longer. Projected 5-year disease-specific survival (71% vs 74%) and freedom from recurrence (69% v. 71%) were nearly identical., Conclusions: Although these selected elderly patients experienced greater myelosuppression and supportive care requirements, outcomes were the same as in younger patients. Age alone should not be considered a contraindication to aggressive chemoradiotherapy for this disease., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate., Methods: A retrospective chart review of neck management in patients after chemoradiation was performed., Results: Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery. Patients were pathologically positive 13.8% and 39.6% of the time after clinical complete or partial response, respectively. Regional recurrence was more frequent in necks with partial clinical (p = .04) or pathologic responses (p < .01) and with primary site recurrences (p < .01)., Conclusions: It is still safest at our institution to perform selective neck dissection on patients with > or = N2 neck disease when initially observed to prevent unsalvageable regional recurrence until more accurate interval assessment tools are confirmed.

Background: Concurrent chemoradiotherapy (CCRT) for locoregionally advanced esophageal or gastroesophageal junction cancer produces high locoregional control rates but suboptimal distant metastatic control (DMC) and overall survival. This phase II study added gefitinib (G) to our previously tested CCRT regimen in an effort to improve these outcomes., Methods: Eligibility required T3, N1, or M1a esophageal or gastroesophageal junction squamous cell or adenocarcinoma staged by esophageal ultrasound and positron emission tomography/computed tomography. Four-day continuous intravenous infusions of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) began on day 1 of preoperative radiation (30 Gy and 1.5 Gy bid). Surgery followed in 4 to 6 weeks, and an identical course of CCRT 6 to 10 weeks postoperatively. G 250 mg/d was given with preoperative CCRT for 4 weeks and restarted with postoperative therapy for 2 years. Results were retrospectively compared with our historical series of 93 patients given CCRT without G., Results: Between April 2003 and July 2006, 80 patients were enrolled. Patient and tumor characteristics were similar to our historical series. G did not increase toxicity except for development of rash in 42 (53%) and diarrhea in 44 (55%) 3-year Kaplan-Meier estimates (G versus non-G treated patients) included: overall survival (42% versus 28%, p = 0.06), DMC (40% versus 32%, p = 0.33), and locoregional control (76% versus 77%, p = 0.74). Intolerance for G maintenance occurred in 48% of patients. Patients who experienced G related diarrhea appeared to have improved outcomes., Conclusions: Although G did not worsen CCRT toxicity, maintenance therapy proved difficult. This contemporary cohort of patients enjoyed superior survival, which does not solely reflect a decrease in DMC and merits further investigation.

Introduction: Mature results are presented from a phase II trial of postoperative concurrent chemoradiotherapy in patients with poor-prognosis cancer of the esophagus and gastroesophageal junction after primary surgical resection., Methods: Resected patients with a pathologic stage of T3, N1, or M1a were eligible for this trial. Concurrent chemoradiotherapy was begun between 6 and 10 weeks after surgery and consisted of radiotherapy (1.8 Gy/d to a planned dose of 50.4-59.4 Gy), concurrent with two cycles of 5-fluorouracil (1000 mg/m/d) and cisplatin (20 mg/m/d), both given as 4-day continuous intravenous infusions during the first and fourth weeks of the radiation., Results: Between 1995 and 2006, 50 patients were enrolled. The median age was 59 (range, 33-76) years, and most patients were male (86%), Caucasian (96%), and had undergone a transthoracic esophagogastrectomy (74%) for what proved to be a node positive (86%) adenocarcinoma (86%). Postoperative concurrent chemoradiotherapy was accompanied by neutropenia requiring hospitalization for fever in only four patients (8%) and no toxic deaths. With a median follow-up of 47 (range, 36-124) months, the Kaplan-Meier 4-year projected overall survival is 51%, freedom from recurrence 50%, distant metastatic control 56%, and locoregional control 86%. An earlier pathologic stage was the only predictor for a better outcome., Conclusions: This schedule of postoperative concurrent chemoradiotherapy has acceptable toxicity for patients with poor-prognosis esophageal and gastroesophageal junction cancer after surgery. Outcomes are better than historical results after surgery alone and justify further investigation of this approach.

Background: Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success., Methods: Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure., Results: The 5-year Kaplan-Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control., Conclusion: Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective., ((c) 2008 Wiley Periodicals, Inc.)

Purpose: Mediastinoscopy is routinely carried out on the majority of nonmetastatic, non-small-cell lung cancer (NSCLC) patients in our institution. We used the results of mediastinoscopy from a Stage III NSCLC cohort to assess the reliability of positron emission tomography (PET) scans at identifying involved mediastinal lymph nodes (MLN) when used during radiotherapy planning., Methods and Materials: Mediastinoscopy was the gold standard. Characteristics of PET were calculated for nodal sensitivity. To compare the impact on contouring, theoretical nodal targets (NTs) containing involved MLNs were generated using PET and mediastinoscopy. We determined whether the NT derived from PET (NT-P) was equivalent to, greater than, or less than that seen with the mediastinoscopy (NT-M)., Results: Data for 122 patients with Stage III NSCLC, treated between 2000 and 2004, were analyzed. After exclusions, 87 patients with Stage III disease by mediastinoscopy were analyzed. Overall PET sensitivity was 61% and positive predictive value was 94%. Of the 87 patients, 33 (38%) had no abnormal MLN findings by PET. Of 36 Stage IIIA cancer patients, 18 (50%) had NT-P equivalent to NT-M, 10 (28%) had smaller NT-Ps, and 8 (22%) had larger NT-Ps compared with NT-Ms. Of 18 Stage IIIB cancer patients, NTs were equivalent in 6 (34%); in 1 patient (5%) NT-P was larger than the corresponding NT-M, and in 11 (61%) smaller than the corresponding NT-M., Conclusions: In this study PET had modest sensitivity to detect MLN involvement and underestimated the extent of involved nodes for target definition. The role of PET in mediastinal contouring needs to be evaluated prospectively and ideally correlated with a pathology standard.

Purpose: Three-dimensional computed tomography-based radiotherapy planning (3DCTP) is increasingly employed in the treatment of esophageal cancer. It is unknown whether a 3DCTP approach influences outcomes compared to two-dimensional planning (2DP). This study compares clinical outcomes for homogeneously treated patient cohorts stratified by planning modality., Methods and Materials: A retrospective chart review was conducted on patients with T3/4 and/or node-positive esophageal carcinoma treated at the Cleveland Clinic between July 1, 2003 and May 31, 2006 who were managed with an institutional regimen consisting of preoperative radiotherapy, whether 3DCTP or 2DP [30 Gy/20 fractions/1.5 Gy twice daily over 2 weeks], with concurrent cisplatin and 5-fluorouracil the first week. Following definitive resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered., Results: One hundred and forty-one patients completed preoperative CRT and were available for review. The median follow-up of living patients is 21.7 months. Fifty-five percent underwent 3DCTP and 45% had 2DP. The treatment groups were similar, with the exception of clinical stage group, with 2DP having more stage II and fewer stage III patients than 3DCTP (p = 0.02). 3DCTP plans had significantly smaller field sizes by area (p < 0.0001). Pathologic response, locoregional control, distant control, and overall survival were equivalent between the two planning modalities. Esophagitis was significantly less common with a 3D approach compared to 2D planning (49% vs. 71%, p = 0.0096), with other toxicities equivalent between the groups., Conclusions: 3DCTP reduces acute esophagitis in patients receiving multimodality therapy for esophageal cancer without compromising clinical outcomes.

Objective: To report our experience using the neck examination, computed tomography (CT), and positron emission tomography (PET) to clinically evaluate node-positive patients with head and neck squamous cell cancer for residual neck node disease after definitive chemoradiotherapy., Design: Retrospective review of all Cleveland Clinic patients with head and neck squamous cell cancer and N2 or N3 neck node involvement at presentation who were treated with definitive concurrent chemoradiotherapy and who underwent clinical restaging after treatment using the neck examination, CT, and PET., Setting: Tertiary care referral institution., Patients: Forty-eight patients with 72 positive necks at diagnosis were followed up for a median of 20 months., Main Outcome Measures: Palpable nodes on examination, nodes larger than 1 cm, nodes with central necrosis on CT, or any hypermetabolic lymph nodes on PET were considered clinical evidence of residual nodal disease. The true rate of pathologic involvement was determined by histologic examination after planned neck dissection or if regional recurrence developed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 3 clinical assessment tools., Results: Planned neck dissection was performed in 33 necks and was positive for residual neck node disease in 5 necks. A delayed neck dissection was performed in 5 necks and was positive in 3 necks. The positive predictive value was low for all 3 clinical assessment tools. The addition of PET did not significantly improve the negative predictive value or positive predictive value of CT and the clinical examination., Conclusions: Residual neck node disease after definitive chemoradiotherapy was infrequent and was not well predicted by PET. A positive PET finding in this setting is of little utility. Although a negative PET finding was highly predictive for control of neck disease after chemoradiotherapy, it added little to the clinical neck examination and CT.

Objectives: This is a report of mature results from a phase II trial of an accelerated multimodality treatment program for locoregionally advanced cancer of the esophagus and gastroesophageal junction with a focus on the impact of clinical heterogeneity on outcomes. A split course of pre- and postoperative hyperfractionated radiation therapy and concurrent chemotherapy was used in an effort to limit perioperative mortality., Methods: Eligibility required a diagnosis of esophageal or gastroesophageal junction cancer and an esophageal ultrasound stage of at least T3, N1, or M1A. Patients received a 12-day induction course of radiation (1.5 Gy twice a dose to a dose of 30 Gy) concurrent with 4-day continuous intravenous infusions of cisplatin (20 mg/m2 per day) and 5-fluorouracil (1000 mg/m2 per day) beginning on day 1. Surgery followed in 4 to 6 weeks followed 6 to 10 weeks later by a second, identical course of chemoradiotherapy., Results: From October 1999 through March 2003, 93 patients were enrolled; 96% were white, 86% male, and 83% had adenocarcinoma. Resection was possible in 83 patients (89%) with 4 (5%) perioperative deaths. With a median follow up of 50 months (range, 34-72 months), the 3-year projected overall survival rate is 27.9%, freedom from recurrence 30.5%, and distant metastatic control 32.4%. Locoregional control in resected patients is 86%. Freedom from recurrence and distant control were significantly better in patients with 1) earlier pretreatment clinical stage, 2) earlier postinduction pathologic stage, 3) squamous cell cancer, and 4) a pathologic response., Conclusions: This accelerated multimodality treatment program is feasible and perioperative mortality proved acceptable. Despite excellent locoregional control, freedom from recurrence, and overall survival proved disappointing reflecting the frequency of distant metastases. Heterogeneity in patient populations makes comparisons with similar nonrandomized experiences problematic.

Background: Concurrent chemoradiation therapy has been demonstrated to be effective as an organ-sparing treatment for select advanced head and neck squamous cell carcinoma (HNSCC). However, this treatment modality is not without side effects. One side effect is the formation of upper esophageal strictures. As concurrent chemoradiation treatment is used more frequently, it is important to identify risk factors associated with stricture formation., Methods: A retrospective chart review of all patients who had undergone definitive concurrent chemoradiation treatment between 1989 and 2002 was performed. Exclusion criteria included death within 1 year or persistent/recurrent disease that required surgical salvage at the primary site. The outcome measure was stricture formation as determined by both objective findings (barium swallow or endoscopy) and the need for dilation after treatment., Results: Of the 222 patients in this cohort, there were enough data for 199 patients to assess for stricture formation. Strictures developed in a total of 41 patients (21%). Significant predictive factors were a twice-daily (BID) radiation fractionation (p = .007), female sex (p = .015), and a hypopharyngeal primary site (p = .01). Age and tumor extent were not significant factors in stricture formation (p = .15 and p = .23, respectively)., Conclusions: Symptomatic strictures occur in 21% of patients undergoing concurrent chemoradiation for HNSCC. Female sex, BID radiation fractionation, and a hypopharyngeal primary site are significant predictive factors for stricture formation., ((c) 2006 Wiley Periodicals, Inc.)

Purpose: This multicentered phase III trial was designed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck cancer undergoing radiation therapy., Patients and Methods: Patients with biopsy-proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of the following treatments: prophylactic trolamine emulsion, interventional trolamine emulsion, or declared institutional preference. The primary outcome was the reduction in grade 2 or higher skin toxicity, as per National Cancer Institute Common Toxicity Criteria version 2.0. Secondary outcomes included patient-reported quality of life (QOL)., Results: From October 2000 to April 2002, 547 patients from 51 institutions were entered onto the trial. The average age was 59 years. Patients were predominately male (79%) and most continued to use tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms of the study, respectively. No significant differences in QOL were found., Conclusion: The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL. The use of 15 different local standards of care highlights the need to continue research that will result in evidence-based recommendations to reduce the burden of radiation dermatitis.

Purpose: A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer., Patients and Methods: Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease., Results: With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors., Conclusion: Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.

Background: Brain metastases are an uncommon complication in women with primary ovarian carcinoma; thus, little is known about whether the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classification system is valid in this patient population., Methods: From September 1985 to June 2002, 19 patients with brain metastases resulting from primary ovarian carcinoma underwent treatment at the Cleveland Clinic Foundation. The medical records of these patients were retrospectively reviewed., Results: At the time of data analysis, all 19 women had died. The median age at diagnosis of primary ovarian carcinoma and brain metastasis was 51 and 54 years of age, respectively. Fifteen patients presented with a Karnofsky performance status (KPS) of 70 or higher. Seven patients had a single brain lesion and 12 had multiple lesions. All RTOG RPA prognostic classes were represented, with median survivals of 24.7, 8.9, and 2.6 months for Classes I, II, and III, respectively (P = 0.31). Patients who underwent surgical resection survived longer than those who did not (33.7 vs. 7.4 mos). The presence of multiple lesions was adversely related to survival on multivariate analysis (P = 0.03). Primary control was an important predictor of survival on multivariate analysis as well (P = 0.01) and was achieved in 15 of the 19 women., Conclusions: This is the first study to support the prognostic usefulness of the RTOG RPA classification for ovarian carcinoma patients with metastasis to the brain. The number of metastatic intracranial lesions should be included when determining the prognosis., (Copyright 2005 American Cancer Society)

There are over 200,000 cases of brain metastases (BrM) every year, but very few are from esophageal cancer primaries. In order to determine predictors for outcome of these patients, the authors conducted a retrospective review of twenty-seven patients with BrM from esophageal carcinoma diagnosed at the Cleveland Clinic Foundation between 1991 and 2001. For the entire cohort, median follow-up and median survival was 3.6 months and 3.6 months, respectively. On univariate analysis, patients with Karnofsky Performance Status (KPS) >/= 70, low recursive partitioning analysis score, single BrM, no systemic disease, and aggressive treatment [surgery, stereotactic radiosurgery (SRS) + whole brain radiation (WBRT), SRS + surgery + WBRT, surgery + WBRT)] had a significantly improved survival. In a multivariate model, patients with higher KPS and aggressive treatment had improved survival. The 1-year survival for the WBRT alone group and the aggressive treatment group was 6%, and 36% respectively. We conclude that based on the data presented here, patients with BrM from esophageal cancer have poor outcome. Aggressive treatment and favorable KPS are associated with longer survival for selected patients. We recommend esophageal cancer patients with BrM be enrolled in clinical trials to better delineate the role of treatment and potentially improve results.

Purpose: Results are reported from an aggressive chemoradiotherapy protocol for advanced squamous cell head and neck cancer., Patients and Methods: Patients with advanced squamous cell head and neck cancer were treated with hyperfractionated radiation therapy (72 Gy at 1.2 Gy twice per day) and two courses of concurrent chemotherapy with fluorouracil (1,000 mg/m(2)/d) and cisplatin (20 mg/m(2)/d), both given as 96-hour continuous intravenous infusions during weeks 1 and 4 of radiation therapy. Primary-site resection was reserved for residual or recurrent primary-site disease after chemoradiotherapy. Neck dissection was considered for N2 or greater disease, irrespective of clinical response, and for residual or recurrent neck disease after nonoperative treatment., Results: Forty-one patients with stage IV disease were treated. Toxicity was significant, with grade 3 to 4 mucositis in 98%, dysphagia in 88%, and skin reaction in 85%. Neutropenic fever requiring hospitalization occurred in 51%. Despite feeding tube placement in 35 patients (85%), the mean weight loss during chemoradiotherapy was 13.3% of initial body weight. One patient died during treatment as a result of a pulmonary embolus. At a median follow-up period of 30 months, the 3-year Kaplan-Meier projected overall survival was 59%, disease-specific survival 69%, likelihood of local control without surgical resection 91%, and local control with surgical resection 97%. The likelihood of distant disease control at 3 years was 74%, and distant metastases were present in eight of 13 patients who died., Conclusion: This chemoradiotherapy schedule produces considerable but manageable toxicity. Survival and organ preservation are excellent for this poor-prognosis patient cohort. Distant metastases are the most common cause of treatment failure.

Background: The incidence of hypothyroidism was assessed retrospectively from a data base of 155 patients with head and neck carcinoma who were treated at the Cleveland Clinic Foundation between 1990 and 1997., Methods: One hundred patients were randomized between radiotherapy (RT) (66-72 grays in single daily fractions) and RT with concurrent chemotherapy (CT) using 5-fluorouracil and cisplatin. An additional 55 patients received RT and CT without randomization. Primary site surgery was performed for tumor persistence or recurrence and included a thyroidectomy in nine patients. These nine patients, along with three patients who had hypothyroidism prior to treatment, were excluded from the analysis. At regular intervals after the completion of treatment, all patients were evaluated for the development of hypothyroidism, defined as a serum thyroid-stimulating hormone (TSH) level > 5.5 microU/mL., Results: With a median follow-up for 143 evaluable patients of 4.4 years (range, 1.5-9.2 years), the 5-year Kaplan-Meier projected incidence rate of hypothyroidism was 48%, and the 8-year projected incidence rate was 67%. The median time to the development of hypothyroidism was 1.4 years (range, 0.3-7.2 years). The likelihood of developing hypothyroidism could not be predicted according to age, gender, primary site, tumor or lymph node status, overall stage, RT dosage to the primary site or to the neck, or inclusion of CT in the treatment plan. Only race proved predictive, with no African-American patients developing hypothyroidism (P = 0.02)., Conclusions: The authors conclude that the incidence rate of hypothyroidism after patients undergo RT for head and neck carcinoma is higher than generally reported and that TSH screening after treatment appears justified., (Copyright 2001 American Cancer Society.)

Background: Multimodality treatments for patients with squamous cell head and neck carcinoma often produce significant mucositis and dysphagia, mandating enteral nutritional support. Patient preference has resulted in the increasing use of percutaneous endoscopic gastrostomy (PEG) tubes rather than nasogastric (NG) tubes. Anecdotal observations of prolonged PEG dependence and of a need for pharyngoesophageal dilatation in PEG patients prompted a retrospective review of the use of both types of feeding tubes., Methods: Patients who were treated on clinical trials of radiotherapy or chemoradiotherapy for squamous cell head and neck carcinoma between 1989 and 1997 were reviewed retrospectively. Data were gathered regarding demographics, primary tumor site, T and N classifications, and the need for feeding tube placement. In patients requiring feeding tubes, the type and duration of the feeding tube, the need for tracheostomy, the need for pharyngoesophageal dilatation, and the degree of mucositis and dysphagia at baseline and at 1 month, 3 months, 6 months, and 12 months after beginning treatment were recorded. Comparisons were then made between the NG and the PEG groups., Results: Ninety-one feeding tubes were placed in 158 patients over the 8-year interval. A hypopharyngeal primary site, female gender, a T4 primary tumor, and treatment with chemoradiotherapy were predictive of a need for feeding tube placement. NG tubes were placed in 29 patients, and PEG tubes were placed in 62 patients. PEG patients had more dysphagia at 3 months (59% vs. 30%, respectively; P = 0.015) and at 6 months (30% vs. 8%, respectively; P = 0.029) than NG patients. The median tube duration was 28 weeks for PEG patients compared with 8 weeks for NG patients, (P < 0.001). Twenty-three percent of PEG patients needed pharyngoesophageal dilatation compared with 4% of NG patients (P = 0.022). These end points could not be correlated with age, stage, primary tumor site, or tracheostomy placement., Conclusions: Although patients treated for head and neck carcinoma find that the PEG tube is a more acceptable route for enteral nutrition than the NG tube, in the authors' experience, a PEG tube was required for longer periods of time and was associated with more persistent dysphagia and an increased need for pharyngoesophageal dilatation. A randomized prospective trial is needed to test these observations., (Copyright 2001 American Cancer Society.)

Radiation therapy is an important treatment option for patients with skull base tumors. It has been proven to be effective as primary or adjunctive therapy. Results with conventional radiation treatments have been good to excellent, with limited morbidity. Despite recent advances in neurosurgery and radiation oncology, conventional radiation therapy continues to play a role for some patients. The use of newer technologies such as radiosurgery, three-dimensional conformal therapy, and intensity-modulated radiation therapy should provide equal or better tumor control with decreased morbidity. Future studies should determine the roles of conventional and more innovative radiation approaches.

Background: The current study presents mature results from a Phase III randomized trial comparing radiation therapy and concurrent chemoradiotherapy in patients with resectable American Joint Committee on Cancer Stage III and IV disease., Methods: One hundred patients were randomized to receive either radiation therapy alone (Arm A) (at a dose of between 66-72 grays [Gy] at 1.8-2 Gy per day) and the identical radiation therapy with concurrent chemotherapy (Arm B) (5-fluorouracil, 1000 mg/m(2)/day, and cisplatin, 20 mg/m(2)/day, both given as continuous intravenous infusions over 4 days beginning on Days 1 and 22 of the radiation therapy). Primary site resection was planned for patients with residual or recurrent local disease. Cervical lymph node dissection was performed for regional persistent disease or recurrence, or if N2-3 disease was present at the time of presentation., Results: After completing all therapy including surgery, 82% of the patients in Arm A and 98% of the patients in Arm B had been rendered disease free (P = 0.02). At a median follow-up of 5 years (range, 3-8 years), the 5-year Kaplan-Meier projections for overall survival for Arm A versus Arm B were 48% versus 50% (P = 0.55). Kaplan-Meier projections for the recurrence free interval were 51% versus 62% (P = 0.04), projections for a distant metastasis free interval were 75% versus 84% (P = 0. 09), projections for overall survival with primary site preservation were 34% versus 42% (P = 0.004), and projections for local control without surgical resection were 45% versus 77% (P < 0.001). Salvage surgery proved to be successful in 63% and 73%, respectively, of the Arm A and Arm B patients with primary site failure. Unrelated death while free of disease occurred in 22% and 32%, respectively, of Arm A and Arm B patients (P = 0.26)., Conclusions: The addition of concurrent chemotherapy to definitive radiation in patients with resectable Stage III and IV squamous cell carcinoma of the head and neck improves the likelihood of disease clearance, a recurrence free interval, and primary site preservation. However, overall survival does not appear to be improved, reflecting both effective surgical salvage after local recurrence and competing causes of death., (Copyright 2000 American Cancer Society.)

Background: Since 1989, 105 patients with squamous head and neck cancer have been treated with combined chemoradiotherapy., Objective: To examine the effectiveness of using combined chemoradiotherapy on patients with squamous head and neck cancer., Design: Eight-year (1989-1997) single-institution evaluation of 105 patients., Methods: Treatment consisted of fluorouracil, 1000 mg/m2 per day, and cisplatin, 20 mg/m2 per day, both given as continuous infusions during 4 days beginning on day 1 and 22 of a concurrent radiotherapy course. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Planned neck dissection was recommended for all patients with N2+ neck disease, irrespective of clinical response., Results: The 105-patient cohort consisted of 79 men and 26 women. The primary site was identified in the oral cavity in 6, oropharynx in 46, larynx in 30, and hypopharynx in 20 patients. Two patients had multiple primaries and 1 patient had an unknown primary. There were 4 patients with stage II, 24 with stage III, and 77 with stage IV disease. Grade 3 and 4 chemoradiotherapy toxic effects included mucositis in 88% of patients, cutaneous reaction in 50%, neutropenia in 49%, thrombocytopenia in 12%, and nausea in 5%. There were no deaths secondary to treatment. The mean weight loss was 12% of initial body weight. To date, primary site persistence or recurrence has occurred in only 14 patients (13%). With a mean follow-up of 39 months, 66 patients (63%) are alive and free of disease. The Kaplan-Meier 4-year projected overall survival is 60% with a disease-specific survival of 74%, a distant metastasis-free survival of 84%, and an overall survival with primary site preserved of 54%., Conclusions: This chemoradiotherapy regimen, although toxic, is tolerable with appropriate supportive intervention. Locoregional and distant control are likely. Primary site conservation is possible in most patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancer.

Objective: To determine the incidence of minor and major complications in patients with squamous cell carcinoma of the upper aerodigestive tract who require surgical salvage or planned neck dissection after an initial treatment regimen with radiotherapy or concurrent chemoradiotherapy for organ preservation., Design: The medical records of 100 patients treated in a phase 3 trial comparing radiotherapy alone with concurrent chemoradiotherapy for stage III and IV head and neck squamous cell carcinoma were reviewed. Fifty-four patients underwent 59 surgical procedures. Twenty-nine planned neck dissections were performed for persistent neck disease or initial stage N2 or greater. For persistent or recurrent disease at the primary site, 30 salvage operations were performed., Setting: Academic tertiary care referral center., Results: Complications occurred in 15 (46%) of the 33 procedures in the radiation-only group and 12 (46%) of the 26 procedures in the chemoradiotherapy group. Major complications occurred in 4 (12%) of the procedures in the radiation-only group and 3 (12%) of the procedures in the chemoradiotherapy group. The incidence of minor complications was 33% and 35% in the radiation-only and chemoradiotherapy groups, respectively. The major complication rate for salvage operations did not differ between the radiation-only and chemoradiotherapy groups (16% and 27%, respectively; P=.79 by chi2 test). The incidence of major complications in planned neck dissections was 7% of the radiation-only group and 0% of the chemoradiotherapy group., Conclusions: After radiation or concurrent chemoradiotherapy, surgery can be performed with an acceptable rate of major complications. Adding chemotherapy did not increase the incidence of surgical complications. These results differ from other reports in the literature.

Background: A phase III randomized comparison of radiotherapy alone versus combination chemotherapy and concurrent continuous-course radiotherapy was performed at the Cleveland Clinic Foundation., Methods: Between March 1990 and June 1995, 100 patients with resectable stage III and IV squamous cell head and neck cancer were randomized to either Arm A: radiotherapy alone, 68-72 Gy at 1.8-2.0 Gy per day; or to Arm B: the identical radiotherapy with concurrent chemotherapy. Chemotherapy consisted of 5-fluorouracil, 1000 mg/m2/day, and cisplatin 20 mg/m2/ day, both given as continuous intravenous infusions over 4 days beginning on day 1 and day 22 of the radiotherapy. At 50-55 Gy, patients were clinically reassessed. If a response was evident, radiotherapy was completed. In non-responding patients, however, radiotherapy was terminated and surgery recommended. After completion of all treatment, salvage surgery was performed, if possible, for any residual primary or nodal disease or for any subsequent locoregional recurrence., Results: Except for an overrepresentation of T1 patients on Arm A, the treatment arms were equivalent. Toxicity was greater in the patients on Arm B with a higher incidence of grade III and IV neutropenia, thrombocytopenia, cutaneous reaction, and mucositis. Feeding tubes were also required more often, and weight loss was greater on the chemotherapy arm. No toxic deaths occurred. With a median follow-up of 36 months, the Kaplan-Meier 3-year projections of relapse-free survival are 52% for Arm A and 67% for Arm B (p = .03), and the likelihood of developing hematogenous metastases is 21% for Arm A and 10% for Arm B (p = .04). Although overall survival is not significantly different, overall survival with successful primary site preservation was 35% for Arm A and 57% for Arm B (p = .02). This difference remains statistically significant in the subsets of patients with laryngeal and hypopharyngeal primaries but not in patients with oropharyngeal primaries., Conclusions: Continuous-course radiotherapy and concurrent combination chemotherapy is an intensive, toxic but tolerable treatment regimen, which, when compared with radio therapy alone, can produce an improvement in relapse-free survival, a decrease in distant metastases, and an improvement in overall survival with successful primary site preservation.

Background: Treating the neck after organ-preservation treatment with radiotherapy or chemoradiotherapy can be problematic., Methods: To develop management guidelines, we reviewed the results of a 100-patient phase-3 trial that had compared outcome after radiotherapy alone with outcome after chemoradiotherapy for head and neck cancer. Patients were randomly assigned to receive radiotherapy alone or concurrent chemoradiotherapy. After completing therapy, patients were reassessed, and surgery was recommended for persistent disease at the primary site or neck and for all patients with stage N2-3 neck nodes regardless of clinical response., Results: Of the 47 patients with stage NO-1, 43 had a complete response (CR); of the 18 N1 patients, all but 4 had a CR. One of these 4, as well as 5 others among the NO-1 patients, underwent neck dissection (n = 6). No disease was found on pathologic examination, and no patient had neck recurrence. Of the remaining 41 N0-1 patients, 3 had disease progression and received no further therapy. Of the 38 others, 4 had neck recurrence, with 3 recurring at the primary site. Of the 53 with stage N2-3, 23 had less than a complete response (

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m2/day and cisplatin 20 mg/m2/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locoregional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.

We report on 2 men and 2 women with locally advanced squamous cell carcinoma of the urethra who were treated with combination chemotherapy and radiation. Treatment consisted of 1,000 mg./M.2 5-fluorouracil plus 15 mg./M.2 mitomycin-C followed by 30 to 50 Gy. external beam radiation. The 2 women achieved durable complete responses, and are alive with no evidence of disease 94 and 43 months later, respectively. The men also had regional lymph node metastases, and 1 achieved complete response and has no evidence of disease 98 months posttreatment, while the other experienced partial response in the primary tumor and complete response in the involved inguinal nodes. The latter patient died of an unrelated cause with residual disease at 7 months. Only mild toxicity occurred in 3 patients. This regimen of chemotherapy and radiation is well tolerated and should be considered as primary therapy for invasive squamous cell carcinoma of the male and female urethra.

Purpose: Endocavitary irradiation delivers high-dose irradiation with limited penetration and is an established modality for the curative treatment of select tumors. The purpose of this study was to review the experience from our institution with endocavitary irradiation., Methods: All patients with rectal cancer treated with endocavitary irradiation between 1973 and 1992 were studied. Collected data included: tumor size, tumor differentiation, distance from the anal verge, mean follow-up, recurrence, and other treatments used., Results: One hundred ninety-nine patients received endocavitary irradiation, with 126 treated with curative intent. No significant differences were found between groups with recurrence and no recurrence when examining tumor size, differentiation, distance from the anal verge, or follow-up. With a mean time to recurrence of 16.1 (range, 1-56) months, 37/126 patients had a recurrence, and 89/126 had no recurrence. Ten recurrences were distant, and all patients died of the disease. Twenty-seven patients had local recurrence. Following additional treatments, 14 additional patients were rendered free of disease., Conclusion: Endocavitary irradiation initially rendered 71 percent (89/126) free of disease. With additional treatment 11 percent (14/126) were rendered free of disease. In the subgroup of patients followed more than five years, 68 percent had no evidence of disease at follow-up after endocavitary irradiation, and 91 percent had no evidence of disease with additional treatment. Tumor size, differentiation, morphology, and distance from the anal verge did not influence recurrence. Debulking or surgical excision before endocavitary irradiation did not increase recurrence. Diligent long-term follow-up and a liberal policy to biopsy suspicious areas may increase the salvage rate.

Concurrent radiation therapy and chemotherapy is a promising approach to the treatment of squamous cell head and neck cancer. Toxicity, however, has required either scheduled breaks in radiation therapy administration or compromise in chemotherapy dose intensity. We describe the toxicity and results in 19 patients treated at diagnosis with a continuous course of radiation therapy and intensive concurrent combination chemotherapy using 5-fluorouracil and cisplatin. Toxicity among these 19 patients was significant, including mucositis, myelosuppression, and weight loss, and aggressive supportive efforts were required. No toxic deaths occurred, however. At the end of treatment, all patients had achieved complete control of their primary-site tumor. Primary-site resection was not required in any patient for tumor control, but neck dissections were performed in selected individuals with involved nodes at diagnosis. No patient recurred at the primary site and only a single patient recurred in the neck. We conclude that this chemoradiotherapy schedule is very effective, albeit toxic. Toxicity, however, can be managed with appropriate aggressive supportive measures. Confirmation of these encouraging treatment results will require performance of a randomized clinical trial.

Background: Previous reports have shown low-dose-rate (LDR) afterloading Ir-192 endobronchial radiation therapy (EnBRT) to effectively palliate symptoms in patients with malignant airway obstruction. The authors retrospectively assessed the consequences of LDR EnBRT with or without neodymium yttrium aluminum garnet (Nd:YAG) laser resection in 37 patients., Methods: Between February 1986 and June 1991, 37 patients with malignant airway obstruction were treated with LDR EnBRT at The Cleveland Clinic Foundation. Inclusion criteria for LDR EnBRT with or without Nd:YAG laser resection were patients with recurrent, symptomatic endobronchial lesions treated previously with external beam irradiation. Of the 37 patients, 21 patients with endobronchial lesions underwent Nd:YAG laser resection; 16 patients with mainly extrinsic lesions received EnBRT only. Before EnBRT, selected patients (7 of 16 in the nonlaser-treatment group and 14 of 21 in the laser-treatment group) received additional external beam treatments of 2000 cGy/10 fractions. The LDR afterloading Ir-192 technique was used to deliver approximately 30 Gy to a 1.0-cm radius target., Results: All patients had one or more of the following symptoms: 1) dyspnea, 2) fever, 3) cough, and 4) hemoptysis. Good-to-excellent symptom relief was apparent in 16 of 21 (76.2%) laser-treated patients and in 12 of 16 (75%) nonlaser-treated patients. Follow-up bronchoscopy in 28 patients revealed tumor regression in 22 (79%). Median survival time was 16.3 weeks in the laser group and 11.7 weeks in the nonlaser group (P = 0.36). Longer median survival times were noted in laser-treated (22.8 weeks) and nonlaser-treated (16.4 weeks) patients receiving additional external beam treatments. Exsanguination occurred in 7 of 21 (33.3%) laser-treated patients and in 4 of 16 (25%) nonlaser-treated patients. The only factor affecting the exsanguination rate was implant location: 6 of 11 (54.5%) patients had lesions in the right or left upper lobe., Conclusions: EnBRT alone or with Nd:YAG laser resection provided good-to-excellent symptom palliation in these patients although a high rate of exsanguination occurred in both groups.

Long-term survival following the diagnosis of ovarian malignant mixed mullerian tumor (MMMT) is unusual. This report analyzes two such long-term survivors. One patient presented with a FIGO Stage III, homologous MMMT treated initially with a combination of surgery and chemotherapy. Residual disease, present at the time of initial operation, responded to the chemotherapy; however, the tumor recurred 2 1/2 years postoperatively. This recurrence responded to a combination of surgery and chemotherapy, including continuous adjuvant chemotherapy. This patient is alive, on maintenance chemotherapy, and without evidence of disease, approximately 7 years after the recurrence and 9 years after the initial presentation. The other patient presented with a FIGO Stage III heterologous MMMT treated initially with combined surgery and chemotherapy. Residual disease was present at the time of initial operation. Persistent pelvic disease led to exploratory laparotomy, excision of an 8-cm diameter pelvic mass, and postoperative radiation therapy. The tumor recurred in the left supraclavicular lymph nodes 2 years later (3 years after the initial presentation). This recurrence responded to radiation therapy. This patient was last seen 2 years later (5 years after the initial presentation). At that time, she was without evidence of recurrence. She died 7 1/2 years after her initial presentation. These two patients represent examples of the unusual occurrence of patients with advanced-stage ovarian MMMT experiencing long-term survival following surgical and adjuvant therapy.

Radiotherapy treatment of patients having a hip prosthesis is a common problem facing dosimetrists and physicists when the treatment plan requires irradiation of the pelvic area. To quantify the perturbation of these devices, attenuation studies were done with 6 and 18 MV photon beams using various hip prostheses models with varying size and composition. These studies have shown that an attenuation of as much as 50% can be found in a single beam profile under the prosthesis. We have studied the capability of a dose planning system to predict the transmission of these devices as compared with measurements.

As a means of increasing local control and disease-free survival in patients with carcinoma of the rectum and rectosigmoid, preoperative and postoperative irradiation therapy have been shown to be effective. The question of the sequence of delivering adjuvant radiation therapy is not settled; however, the benefits and deficits of irradiation therapy as an adjuvant to surgery preoperative or post-operative are reviewed. Basic principles of radiation oncology affecting the selection of the sequence and technique of treatment are discussed.

From July 1979 through March 1984 the Radiation Therapy Oncology Group conducted a randomized study comparing fast neutron radiotherapy versus mixed beam (neutron/photon) radiotherapy versus conventional radiotherapy for patients with non-small cell carcinoma of the lung. Patients were either medically or technically inoperable. One hundred two evaluable patients were placed on the study. The radiation doses were approximately 60 Gy-equivalent on each arm. Patients were stratified according to size of primary, histology, Karnofsky performance status, and age distribution. Overall local response rates as measured by serial radiographs were the same on the three arms, and an actuarial analysis showed no significant differences in either median or long-term survival. However, for the subgroup of patients exhibiting a complete or partial tumor response at 6 months there was a suggestion of improved 3-year survival on the two experimental arms (mixed beam, 37%; neutrons, 25%; photons, 12%). The p value for the difference between the mixed beam and photon curves is 0.14 (two-sided test). The incidence of major complications was higher on the neutron and mixed beam arms. These complications included four cases of myelitis which are analyzed in detail. The results are placed in the context of other published work on the use of neutrons in the treatment of lung cancer.

Between 1980-84, the Radiation Therapy Oncology Group conducted a trial in patients with untreated, unresectable localized carcinomas of the pancreas. Patients were randomly chosen to receive either 6,400 cGy with photons, the equivalent dose with a combination of photons and neutrons (mixed-beam irradiation), or neutrons alone. A total of 49 cases were evaluable, of which 23 were treated with photons, 11 with mixed-beam therapy, and 15 with neutrons alone. The median survival time was 5.6 months with neutrons, 7.8 months with mixed-beam radiation, and 8.3 months with photons. The median local control time was 6.7 months with neutrons, 6.5 months with mixed-beam radiation, and 2.6 months with photons. These differences are not statistically significant. Evidence of moderate-to-life-threatening gastrointestinal or hepatic injury was present in three patients treated with neutrons and one patient treated with photons. The causes of this apparent difference are discussed. This study demonstrates there is no evidence to suggest that neutron irradiation, either alone or in combination with photon irradiation, produces better local control or survival rates than photon irradiation.

In a retrospective review, 62 patients treated for rectal cancer by contact (endocavitary) irradiation at The Cleveland Clinic Foundation were analyzed. This treatment modality delivers high dose, low penetration irradiation to a rectal cancer by direct contact of a 50 KV x-ray source through a special proctoscope. Cancers selected for this treatment include small (3 cm or less), mobile tumors without presacral lymphadenopathy that are within reach of digital examination and are well- or moderately well-differentiated adenocarcinomas. Between 1973 and 1984, 62 patients (37 males, 25 females) were treated--46 by contact irradiation alone and 16 by contact irradiation after excisional biopsy. The median tumor dose was 12,000 rads administered in four fractions at monthly intervals. Mean follow-up was 31 months. Fifty-six patients (90 percent) were disease-free at the time of review or death (ten died from unrelated causes). Eleven patients (18 percent) developed local recurrence but eight of these without distant metastases were rendered disease-free by other treatment--six by surgical resection and two by further radiotherapy. Mean time since secondary treatment is 20 months. Three patients are alive with incurable disease and three have died from cancer--in three of these six patients there was no evidence of local disease. Ulcerated tumors developed local recurrence in five of 17 cases (29 percent) while polypoid tumors recurred locally in six cases (14 percent). Morbidity from the treatment was minor in nature. It is suggested that contact (endocavitary) irradiation is effective treatment for carefully selected cases of rectal cancer.