It is not just IMRT: Human papillomavirus related oropharynx squamous cell carcinoma is associated with better swallowing outcomes after definitive chemoradiotherapy.

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.

Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials.

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.

Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

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.

Hypothyroidism: a frequent event after radiotherapy and after radiotherapy with chemotherapy for patients with head and neck carcinoma.

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.

Enteral nutrition during the treatment of head and neck carcinoma: is a percutaneous endoscopic gastrostomy tube preferable to a nasogastric tube?

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.

Conventional radiation therapy for skull base tumors: an overview.

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.

Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck.

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.

Aggressive concurrent chemoradiotherapy for squamous cell head and neck cancer: an 8-year single-institution experience.

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.

Comparison of surgical complications after organ-preservation therapy in patients with stage III or IV squamous cell 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.

Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer.

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 (

A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results.

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.

Concurrent chemoradiotherapy for salvage in relapsed squamous cell head and neck cancer.

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.

Combination radiation and chemotherapy for the treatment of squamous cell carcinoma of the male and female urethra.

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.

Endocavitary irradiation. An option in select patients with rectal cancer.

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.

Continuous course radiation therapy and concurrent combination chemotherapy for squamous cell head and neck cancer.

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.

Endobronchial radiation therapy with or without neodymium yttrium aluminum garnet laser resection for managing malignant airway obstruction.

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.

Malignant mixed mullerian tumors of the ovary. An analysis of two long-term survivors.

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.

Influence of hip prostheses on high energy photon dose distributions.

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.

Evaluation of neutron irradiation of pancreatic cancer. Results of a randomized Radiation Therapy Oncology Group clinical trial.

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.

Definitive management of rectal cancer by contact (endocavitary) 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.