Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy.

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.

Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx.

PURPOSE: A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS: One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS: The 2-year local control rate for patients who presented with a hemoglobin level < or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P < .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P < .0001). CONCLUSION: Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.

Evaluation and treatment of patients receiving radiation for cancer of the rectum or sigmoid colon in the United States: results of the 1988-1989 Patterns of Care Study process survey.

PURPOSE: For the first time, a Patterns of Care Study (PCS) was conducted in 1989 to determine the national practice standards of radiation oncologists in evaluating and treating adenocarcinoma of the rectum and sigmoid colon. MATERIALS AND METHODS: A national survey of 73 institutions using two-stage cluster sampling was conducted, and specific information on 408 patients from 69 facilities with adenocarcinoma of the rectum and sigmoid colon who received radiation as part of definitive or adjuvant management was collected. RESULTS: Using the modified Astler-Coller (MAC) pathologic staging system, the stage distribution was as follows: A, 0.5%; B1, 4.4%; B2, 23.5%; B3, 5.1%; C1, 8.9%; C2, 30.2%; and C3, 6.6%. Preoperative radiation was used in 29% of patients, but the total dose was greater than 40 Gy in only 20%. Seventy-three percent of patients received postoperative radiation, with approximately 4% receiving combined preoperative and postoperative radiation. Chemotherapy was administered to 44% of patients overall, representing 55% of patients with disease through the bowel wall and/or involving lymph nodes. Only 37% of all patients received chemotherapy concurrent with radiation. An abdominoperineal resection was used in 43%; a low anterior resection was used in 43% as well, while 5% underwent other types of bowel resection. Approximately 8% of patients were treated with a local curative procedure less than bowel resection (eg, local excision, endoscopic resection, fulguration, or contact radiation). At least one third of patients had interruption in their pelvic irradiation of greater than 3 days. There was no statistically significant difference in the frequency of treatment interruptions by dose per fraction or whether chemotherapy was given concurrent with radiation. There was no significant difference in total dose delivered to patients staged B2 and higher treated without chemotherapy compared with concurrent chemotherapy and radiation. Also, there was no significant difference in total dose delivered to patients with B1 and B2, or C1 and C2 versus B3 or C3 cancer. CONCLUSION: This study was conducted on patients treated just before the 1990 National Institutes of Health consensus guidelines issued on the management of colon and rectal cancer. This study indicates that the minority of patients treated with radiation in 1988 and 1989 received concurrent chemoradiation, as currently recommended. Additionally, insofar as present studies are investigating important issues such as the use of sphincter-sparing procedures, preoperative radiation and chemotherapy, and the importance of radiation dose and scheduling with chemotherapy, the information provided by this study will serve as a useful baseline to track future changes in rectal cancer evaluation and management.

Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study.

PURPOSE: Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS: Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m2). RESULTS: Posttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates were lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59%; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not been observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P < or = .001). Of 24 assessable patients who underwent salvage CR, 12 (50%) were rendered disease-free. CONCLUSION: Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.

Radiation therapy for rectosigmoid and rectal cancer: results of the 1992-1994 Patterns of Care process survey.

PURPOSE: To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. MATERIALS AND METHODS: A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. RESULTS: Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. CONCLUSION: Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.

Outcome of patients receiving radiation for cancer of the esophagus: results of the 1992-1994 Patterns of Care Study.

PURPOSE: A Patterns of Care Study examined the records of patients with esophageal cancer (EC) treated with radiation in 1992 through 1994 to determine the national practice processes of care and outcomes and to compare the results with those of clinical trials. PATIENTS AND METHODS: A national survey of 63 institutions was conducted using two-stage cluster sampling, and specific information was collected on 400 patients with squamous cell (62%) or adenocarcinoma (37%) of the thoracic esophagus who received radiation therapy (RT) as part of primary or adjuvant treatment. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Fifteen percent of patients had clinical stage (CS) I disease, 40% had CS II disease, and 30% had CS III disease. Twenty-six percent of patients underwent esophagectomy. Seventy-five percent of patients received chemotherapy; 84% of these received concurrent chemotherapy and radiation (CRT). RESULTS: Significant variables for overall survival in multivariate analysis include the use of esophagectomy (risk ratio [RR] = 0.62), the use of chemotherapy (RR = 0.63), Karnofsky performance status (KPS) greater than 80 (RR = 0.61), CS I or II disease (RR = 0.66), and facility type (RR = 0.72). Age, sex, and histology were not significant. Preoperative CRT resulted in a nonsignificantly higher 2-year survival rate compared with definitive CRT alone (63% v 39%; P =.11), whereas 2-year survival by planned treatment rather than treatment given was 47.7% for preoperative CRT and 35.4% for definitive CRT (P =.23). Definitive CRT compared with definitive RT alone resulted in significantly higher 2-year survival (39% v 20.6%; P =.027) and lower 2-year local regional failure (30% v 57.9%; P =. 0031). CONCLUSION: This study confirms the value of CRT in EC treatment. It indicates that the results obtained in practice settings nationwide are similar to those obtained in clinical trials and that KPS and the 1983 clinical staging system are useful prognostic indicators. The suggested value of esophagectomy and superiority of preoperative CRT over CRT alone in this study should be tested in a randomized trial.

Fractionation and outcomes with palliative radiation therapy.

A dose-response relationship can be established for local control of a variety of malignancies treated with radiation, yet palliation of symptoms oftentimes does not have a clear dose-response relationship. It is important that palliation be achieved with as efficient a fractionation schedule as possible in patients with limited life expectancy and with as few side effects as possible. This article reviews the literature addressing optimal schedules of radiation for palliation based on prognostic factors.

Combined-modality therapy for esophageal cancer: phase I trial of escalating doses of paclitaxel in combination with cisplatin, 5-fluorouracil, and high-dose radiation before esophagectomy.

Several recent reports support administering preoperative chemotherapy and radiotherapy to improve the outcome of patients with resectable esophageal malignancies. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), 5-fluorouracil (5-FU), and cisplatin are known radiosensitizers, and paclitaxel has demonstrated single-agent activity in patients with metastatic esophageal cancer. This study sought to define the maximum tolerated dose of paclitaxel given with 5-FU, cisplatin, and 60 Gy radiotherapy before esophagectomy to patients with potentially resectable lesions. Seventeen patients so treated underwent esophagectomy. Three patients with metastatic disease, treated to obtain more information about the toxicity of the combined-modality regimen, did not undergo surgery. Over 6 weeks, 60 Gy radiation was administered in 2-Gy fractions. During radiation treatment, continuous intravenous infusions of 5-FU 225 mg/m2/d were administered, with paclitaxel given weekly as a 1-hour intravenous infusion immediately preceding a 1-hour cisplatin infusion. Surgery was performed 4 to 6 weeks after the completion of radiotherapy. The 27 patients, one of whom was a woman, had a median age of 58 years and an Eastern Cooperative Oncology Group performance status of 0 (10 patients) or 1. Three patients had a squamous cell histology, while 22 had adenocarcinoma; two had other histologies. The paclitaxel dose levels were 25 mg/m2 in four patients, 40 mg/m2 in five patients, 60 mg/m2 in nine patients, and paclitaxel 50 mg/m2 with 5-FU reduced to 200 mg/m2 in nine patients. The latter proved to be the maximum tolerated dose combination, with cisplatin held constant at 25 mg/m2. This level represents weekly dose intensities of 9.6 Gy radiation, 48 mg/m2 paclitaxel, 24 mg/m2 cisplatin, and 192 mg/m2 5-FU. Diarrhea in four patients, mucositis and dehydration in seven, electrolyte wasting in two, gram-positive catheter-related infection in three, and neuropathy in one proved dose limiting. Hematologic toxicity was relatively mild, with three episodes of nonneutropenic bacteremia, one of which was fatal. Postoperative chemotherapy consisting of four cycles of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75 mg/m2 over 1 hour every 3 weeks was planned but rarely feasible due to postoperative morbidity and poor tolerability of postoperative chemotherapy. Therefore, the use of two induction cycles of this regimen given before the combined-modality study regimen is currently being investigated. Of 17 patients whose surgical specimens were assessed pathologically, three had complete remissions and 14 had partial remissions, five of which were characterized as very good, showing only microscopic foci and marked radiation effects. The median follow-up of the 17 patients who underwent surgery is 50 weeks (range, 5 to 111 weeks). Three relapses occurred at 26, 33, and 43 weeks. We conclude that this is an intense combined-modality preoperative regimen for patients with esophageal cancer. Determining the efficacy of this regimen will require further follow-up and the performance of phase II trials.

The role of radiation therapy in the treatment of brain metastases.

Whole brain irradiation is the most effective means for treating the patient with brain metastases with symptom relief occurring in 70 to 90% of patients. However, 25-50% of patients with brain metastases will die due to eventual failure in the brain and therefore entry of patients into investigative trials is essential for continued progress in the management of this problem. For the patient who is not part of an investigative trial, short courses of radiation of 20 Gy in 1 week or 30 Gy in 2 weeks are generally as effective as more prolonged courses and even shorter courses of treatment could be considered, particularly for the patient with an estimated survival of only 5-6 weeks. The importance of the treatment of brain metastases on the practice of radiation oncology is significant and comparable to other major cancers treated with radiation. It is critical that radiation oncologists can apply this treatment modality in a cost effective manner with careful consideration for the patients' quality of life.

The need for subspecialization: intraoperative radiation therapy.

Intraoperative radiation therapy represents a technically complex branch of radiation oncology which is undergoing intensive study. Further results of randomized Phase III trials must be available before IORT is established as an effective modality. The majority of residency training programs do not have IORT available and the use of IORT is not required for initial certification in radiation oncology. Residents could be educated in the principal concepts and the technical details of IORT and should be knowledgeable in the results of clinical trials in IORT. At the present time the leading investigators in IORT should consider offering a special research year or fellowship training in an appropriate residency training facility. If Phase III trials of IORT prove positive in a number of sites it is likely that this modality will become mainstream and then training in IORT should be required of all radiation oncology residents. Certainly there is insufficient evidence for subspecialty certification in IORT at the present time. However, one should not construe from this statement that special training in IORT is not required for its appropriate use. On the contrary, given the potential for morbidity and yet to be proven efficacy, special training in IORT should be undertaken in centers of excellence in IORT and patients treated with IORT should be entered in clinical trials whenever possible.

Complications from large field intermediate dose infradiaphragmatic radiation: an analysis of the patterns of care outcome studies for Hodgkin's disease and seminoma.

There are only infrequent complications from intermediate dose infradiaphragmatic radiation to the para-aortics or para-aortic and iliac nodal regions as given in Hodgkin's disease or seminoma. Nonetheless, such complications can cause significant debility and may be lifelong. Treatment related factors associated with such complications should be identified and where possible, avoided. We have analyzed the records of 1,026 patients treated nationwide in the Patterns of Care Outcome. Studies including the Hodgkin's national practice survey (387 patients), Hodgkin's large facility survey (253 patients), and Seminoma national practice survey (386 patients). There were 883 patients who received infradiaphragmatic radiation to the para-aortics or para-aortic and iliac regions. Complications which occurred in these patients included gastrointestinal injury, hepatitis, nephritis, gonadal injury, hematopoietic injury, second malignancy, and miscellaneous others. There were 139 complications of any severity and 35 major complications requiring hospitalization for management. The 3-year actuarial complication rates were 14% and 4% for any and major complications, respectively. There was a statistically significant increase in both any complications and major complications with dose (p less than .01). The most frequent complications were those related to gastrointestinal injury such as peptic ulceration, hemorrhage, chronic diarrhea, and intestinal obstruction. Major bowel complications comprised 60% (21/35) of major complications and increased with dose from 1% for doses less than 3,500 cGy to 3% for doses greater than or equal to 3,500 cGy (p = .03). This study indicates that total dose is an important factor in determining complications, particularly gastrointestinal injury, in patients receiving infradiaphragmatic radiation in Hodgkin's disease and seminoma and that prior G.I. disease is associated with an increased risk of radiation related bowel complication. The radiotherapist should seek to optimize the therapeutic ratio in these diseases where gross disease can be controlled with 3500 cGy or less with few exceptions.

Anatomy of the celiac axis and superior mesenteric artery and its significance in radiation therapy.

PURPOSE: In the radiation therapy of upper gastrointestinal malignancies, treatment of lymph nodes in the region of the celiac axis and superior mesenteric axis is often mandated. This study was undertaken to determine the relationship of the celiac axis and superior mesenteric arteries to the vertebral bodies--the radiographically visualized reference structures during simulation. METHODS AND MATERIALS: Twenty-three celiac angiograms and 24 superior mesenteric angiograms performed preoperatively in 24 patients treated at the University of Pennsylvania from 1984 to 1989 for pancreatic carcinoma were examined. The location of the origin of the celiac and superior mesenteric arteries was determined in each case. RESULTS: In 48% of the celiac angiograms, the celiac axis arose from the aorta high at the pedicle of the T-12 vertebral body, contrary to the common belief that the celiac axis arises near the T12-L1 interspace. The superior mesenteric artery arose at the level of L-1 in 83% of the 24 angiograms and below the pedicle of L-1 in 5 (21%). However, none arose below the L1-2 interspace. CONCLUSION: The variability demonstrated in the levels from which these vessels arise strongly suggests individualized treatment planning, including angiographic, CT or MRI data should be performed if tight margins are used. These studies would additionally optimize treatment of the tumor bed. Consideration for dose at field edges (i.e., "buildup") and day to day variation in set-up is required in determining the field borders. Treatment volumes tightly encompassing T12 and L1 could risk undertreating regional lymph nodes associated with these vessels.

Spinal cord protection during radiation therapy.

Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry angle is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature.

Harvesting backscatter electrons for radiation therapy.

PURPOSE: An innovative technique is used to harvest backscatter electrons for the treatment of superficial small lesions of skin, oral cavity, and rectum where a significant dose gradient and maximum surface dose is desired. METHODS AND MATERIALS: Backscatter electrons are harvested out of the primary electron beams from the linear accelerators. The design consists of a short cylindrical cone that fits snugly over a long cylindrical electron cone. The short cylindrical cone has a thick circular plate of high atomic number medium (Pb) attached to the distal end, and a lateral slit of variable length and width. The width of the slit could be closed as desired by rotating the two cones and the length can be increased by lowering the short cylindrical cone. Primary electrons strike the Pb plate perpendicularly and produce backscatter electrons that pass through the lateral slit for treatment. Using film and a parallel plate ion chamber, backscattered electron dose characteristics are studied. RESULTS: The depth dose characteristic of the backscatter electron is very similar to that of the 0.2 mm Al half-value layer x-ray beam that is commonly used for the intracavitary and superficial lesions. The backscatter electron energy is nearly constant and effectively < or = 1 MeV from the clinical megavoltage beams. The backscatter electron dose rate of 0.32-0.8 Gy/min could be achieved from modern accelerators without any modification. The beam flatness is dependent on the slit size and the depth of treatment, but is satisfactory to treat small lesions. CONCLUSIONS: The measured data for backscatter electron energy, fluence, depth dose, flatness, dose rate, and absolute dose indicates that the harvested backscattered electrons are suitable for clinical use.

Prognostic factors in patients with early stage non-Hodgkin's lymphomas of the head and neck treated with definitive irradiation.

Between 1974 and 1989, 58 patients with clinical Stages I and II non-Hodgkin's lymphomas of the head and neck were treated with radiation at the Fox Chase Cancer Center. Forty-one treated with radiotherapy alone form the basis for this retrospective analysis of outcome and prognostic factors. With a mean radiation dose of 4400 cGy, the 5-year actuarial local control rate is 92%. Only one patient failed within an irradiated field. The 5-year actuarial survival and relapse-free survival rates are 85% and 54%, respectively. In a univariate analysis, poor survival was significantly correlated with involvement of Waldeyer's ring, postoperative tumor size greater than 3 cm, and greater than two involved lymph nodes and extranodal sites (p less than 0.02). No such correlations were seen for stage, histologic grade, the presence of extranodal disease, or any of the other parameters that were examined. Relapse free survival was significantly correlated only with the total of the number of involved nodes and extranodal sites. Patients with one or two involved nodes and sites had a 68% chance of remaining disease-free at 5 years compared to 0% for patients with greater than two (p = .02). Again, significant trends were not seen for the other parameters analyzed. These data demonstrate excellent local control, survival, and relapse-free survival using radiation alone with doses of 3000-5000 cGy. In our group of clinically staged patients preselected for treatment with radiation alone, the total of the number of involved nodes and extranodal sites, involvement of Waldeyer's ring, and tumor size after resection correlated strongly with relapse-free survival and overall survival. In patients with early stage non-Hodgkin's lymphomas of the head and neck, initial management with external beam radiotherapy should be considered in particular for those with one or two involved nodes and extranodal sites that are less than 3 cm following resection and that do not involve Waldeyer's ring.

Tumor and treatment factors improving outcome in stage III-B cervix cancer.

This report reviews 271 patients with Stage III-B squamous cell cancer of the uterine cervix from three national surveys conducted by the Patterns of Care Study. A progressive increase in local control and survival is seen among the three surveys which parallels a progressive increase in paracentral (point A) dose and use of intracavitary treatment. Multivariate analysis reveals extent of pelvic disease (unilateral sidewall vs. bilateral sidewall vs. lower 1/3 vagina) and use of intracavitary treatment to be the only significant tumor and treatment factors associated with local control and survival. With aggressive radiotherapy, local control rates exceeding 65% and survival of 50% at 4 years can be anticipated at the expense of a small increase in complications.

Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: a final report of the 1973 and 1978 patterns of care studies.

The Patterns of Care Study (PCS) conducted two national surveys of patients treated in 1973 and 1978 for squamous cell cancer of the uterine cervix. In addition, a survey of patients treated in 1973 from selected large facilities was conducted to establish outcome with "optimal" radiotherapy. The large facility survey consistently reported improved outcome compared to both national average surveys when analyzed by stage and other significant pretreatment factors. That improved outcome was associated with the paracentral (PCS point A) dose and the use of intracavitary irradiation. In this study, we report the pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix by analysis of the 1973 and 1978 PCS data. Pretreatment factors associated with improved pelvic control in multivariate analysis include higher Karnofsky Performance Status (KPS) (Stage I and II), older age (Stage I and II), unilateral parametrial involvement (Stage IIB), and unilateral sidewall involvement (Stage III). The only treatment factor associated with improved pelvic control in multivariate analysis is the use of intracavitary irradiation. However, a dose response for infield pelvic control was demonstrated only in Stage III cervix cancer with the highest rate of pelvic control with paracentral (PCS point A) dose greater than 8500 cGy. Multivariate analysis revealed that unilateral parametrial involvement for Stage IIB and unilateral sidewall involvement for Stage III are significant positive prognostic factors with respect to survival after treatment with radiotherapy. No FIGO substage significantly affected survival after radiotherapy. Although FIGO staging is the single most important pretreatment prognostic factor with respect to survival and infield pelvic failure, FIGO substaging deserves reappraisal and further refinement. Major complications were seen in only 9.5% of patients treated with radiotherapy and were stage but not survey related. There is a significant relationship between PCS point A dose and complications with the highest rate of complications for PCS point A dose greater than 8500 cGy. A significant relationship between lateral (external iliac lymph nodes or PCS point P) dose and major complications is also found, and doses greater than 5000 cGy are associated with a significant increase in complications. The PCS has established two sequential national benchmarks of treatment outcome for squamous cell carcinoma of the uterine cervix treated with radiotherapy with respect to survival, infield pelvic control, and complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Late effects of radiation therapy on the gastrointestinal tract.

Late gastrointestinal complications of radiation therapy have been recognized but not extensively studied. In this paper, the late effects of radiation on three gastrointestinal sites, the esophagus, the stomach, and the bowel, are described. Esophageal dysmotility and benign stricture following esophageal irradiation are predominantly a result of damage to the esophageal wall, although mucosal ulcerations also may persist following high-dose radiation. The major late morbidity following gastric irradiation is gastric ulceration caused by mucosal destruction. Late radiation injury to the bowel, which may result in bleeding, frequency, fistula formation, and, particularly in small bowel, obstruction, is caused by damage to the entire thickness of the bowel wall, and predisposing factors have been identified. For each site a description of the pathogenesis, clinical findings, and present management is offered. Simple and reproducible endpoint scales for late toxicity measurement were developed and are presented for each of the three gastrointestinal organs. Factors important in analyzing late complications and future considerations in evaluation and management of radiation-related gastrointestinal injury are discussed.

Recent patterns of growth in radiation therapy facilities in the United States: a patterns of care study report.

The Patterns of Care Study conducted its seventh survey of radiation oncology facilities with megavoltage equipment. The aims were to identify the basic structural characteristics of the radiation oncology specialty, to allow comparison with previous surveys, to identify trends in the patterns of equipment and personnel usage, and to measure the capabilities of facilities to deliver modern radiotherapy. All radiation oncology facilities in the United States and Puerto Rico were surveyed. Multiple mailings and calls yielded identification of and responses from virtually all facilities doing megavoltage radiotherapy. The survey collected information on equipment, patient load, personnel, and types of procedures performed. The complete census was reviewed, summarized, and compared to previous surveys. Results for 1990 showed 1321 facilities, (938 hospital based, 350 freestanding, 33 federal), 492120 new patients, and 2397 treatment machines (1893 linear accelerators or betatrons and 504 cobalt machines). The number of facilities and total machines increased rapidly with most of the increase in facilities occurring in the freestanding category. The number of cobalt units declined, while the number of linear accelerators increased. The results also showed that 6% of facilities did not have the capability of simulating patients and 7% of facilities did not have treatment planning capability. Of all facilities 9% reported doing intraoperative radiation therapy and 18% doing hyperthermia. For recent years in the specialty of radiation oncology the number of facilities and treatment machines increased at a more rapid rate than the number of new patients.

Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy.

PURPOSE: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma and has been shown to have some utility in predicting outcome in surgically treated patients. The purpose of this study was to evaluate its usefulness as a prognostic indicator in patients treated with radiotherapy. MATERIALS AND METHODS: A retrospective review of all patients treated with radiotherapy of definitive intent (n = 104) for carcinoma of the pancreas at Fox Chase Cancer Center from 1980-1994 was undertaken. Patients were categorized into four groups: Planned preoperative radiation with resection (n = 25); planned preoperative radiation without successful resection (n = 35); postoperative radiation (n = 21); and radiation without planned resection (n = 23). For each group, except those treated without planned resection, median dose for external beam radiotherapy was 50.4 Gy (range = 21.6-63.0 Gy). Those in the remaining fourth group were treated with a median dose of 55.8 Gy (range = 36.0-60.4 Gy). 97% of patients in the first three groups were also treated with 5-FU-based chemotherapy, as were 61% of those in the fourth group. Pretreatment and follow-up CA 19-9 levels were available for 69 patients. RESULTS: Median survival time for all groups was 10 months (range = 1-67 months). Univariate analysis showed significant differences in survival among the groups: Preop with resection 22 months; preop without resection 10 months, postop 17 months; and without planned resection 12 months (p = 0.0005). Overall, patients who underwent resection had a median survival time of 19 months, compared to 11 months in those who did not (p = 0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic indicator on univariate analysis, with a median survival time of 8 months in those having a level greater than the median of 680 U/ml, compared to 20 months in those who did not (p = 0.0003). Similarly, the posttreatment nadir was significant, with a median survival time of 11 months in those with levels above the median of 162.5 U/ml, vs. 26 months in those with levels below 162.5 U/ml (p = 0.001). The median survival time for patients whose CA 19-9 levels decreased in response to treatment by more than 75% was 23 months (range = 6-34 months) vs. 8 months (range = 3-21) in those with 75% or less response (p = 0.003). On stepwise multivariate analysis, pretreatment CA 19-9 level was found to be a significant predictor of survival (p = 0.005). Other potential indicators of outcome, including age, gender, KPS, prediagnosis weight loss, location of tumor, clinical TNM staging, size of lesion, vascular involvement on angiography, and sequence of radiation with respect to resection, were evaluated and were not found to be significant. CONCLUSION: CA 19-9 was demonstrated to be a useful prognostic indicator in patients treated with radiotherapy; other, more traditional, indicators of outcome were of less utility.