Radiotherapy for pediatric brain stem glioma: radiation dose, response, and survival.

An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested.     

Chemotherapy rapidly alternating with accelerated radiotherapy for advanced carcinomas of the hypopharynx and upper esophagus: a feasibility study

Patients with advanced carcinomas of the hypopharynx or upper esophagus have among the worst prognoses in head and neck oncology. We developed a treatment regimen of rapidly alternating multi-agent chemotherapy and accelerated interrupted radiotherapy as follows: Three cycles of chemotherapy were delivered [day 1, cisplatin 100 mg/m2; days 1-4, 5-fluorouracil (5-Fu) 900 mg/m2] and repeated every 3 weeks. On day 8 of each chemotherapy cycle radiotherapy was started, consisting of 10 fractions of 200 cGy delivered twice daily, for 5 days. The total dose of radiotherapy was 6,000 cGy over 7 weeks, and the total duration of chemotherapy and radiotherapy was 8 weeks. Nineteen patients with locally advanced, epidermoid carcinoma of the hypopharynx (9 patients) or upper esophagus (10 patients) were treated on this protocol. Minimum follow-up was 1 year. Twelve patients had tumors judged technically unresectable, whereas 7 had tumors considered resectable only with total laryngectomy, which was unacceptable to the patients. One patient died of nadir sepsis during treatment, but otherwise the acute toxicity was relatively mild (grade I/II in 16 patients, grade III/IV in 3 patients). The complete response rate was 83% (15 of 18 patients), and the partial response rate was 17% (3 of 18). No patient failed to respond. The survival rate was 80% at 1 year and 73% at 18 months. At 1 year, 89% of the patients remained in remission and at 18 months, 74% Late complications occurred in 4 patients. These included laryngeal necrosis, pneumonitis, esophageal stricture, and tracheoesophageal fistula.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiotherapy for pain relief in locally recurrent colorectal cancer.

Eighteen patients with local recurrence of colorectal cancer have been treated by external beam radiotherapy for pain relief. Seven received a fractionated course of 4500cGy and the remainder received single fractions of 1000cGy, a number being treated more than once. The median survival for all patients once recurrence had produced pain was 7 months. Treatment benefit was recorded in 71% treated by fractionated courses and in 66% by single fractions. The duration of pain relief was 3 months for each method. The repeatability of single fraction treatment indicates that this is a worthwhile alternative technique, particularly for those in poor general condition.     

Soft tissue carcinoma. Epidemiology, diagnostics and therapy

The treatment of soft tissue sarcoma requires an individually tailored, multimodal therapy due to the high variability in the clinical situation. Resection is the usual treatment for patients with superficial, low grade tumors with a diameter of <5 cm. For intermediate grade, differentiated lesions, resection with negative resection edges combined with radiotherapy attains an almost 80% total survival rate. For patients with high grade sarcoma of >5 cm, local control can be attained by resection and radiotherapy, however every second patient will develop metastases. Patients with a local recurrence should consider a new resection. Radiotherapy is the more effective the lower the remaining postoperative tumor burden.     

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.     

Evaluation of preoperative radiation therapy in operable colorectal cancer.

MATERIALS AND METHODS: Patients with operable colorectal cancer in the ascending colon, descending colon, and rectum were randomized to 500 cGy before definitive surgery. Patients with stage A and B1 lesions received no further treatment. All patients with stage B2, B3, C1, C2, and C3 received a minimum of 4500 cGy postoperatively. RESULTS: Three hundred fifty-three patients were registered for the study. Three hundred one patients were available for analyses. Follow-up was a minimum of 5 years on all study patients. The majority of patients had rectal cancer. Complications of treatment were acceptable. Two hundred thirty-one patients had stage B2, B3, C1, C2, or C3 tumors. Estimated 5-year rates for no preoperative therapy versus preoperative therapy were as follows: local recurrence 29% versus 26%; metastasis 41% versus 43%; and survival 54% versus 54%. No statistical benefit was observed for preoperative treatment. CONCLUSIONS: In a prospective randomized trial designed to test the value of low-dose preoperative irradiation followed by surgery and postoperative irradiation, the authors were unable to observe any benefit to low-dose preoperative therapy in patients with unfavorable stages.     

Weichteilsarkome

The treatment of soft tissue sarcoma requires an individually tailored, multimodal therapy due to the high variability in the clinical situation. Resection is the usual treatment for patients with superficial, low grade tumors with a diameter of <5 cm. For intermediate grade, differentiated lesions, resection with negative resection edges combined with radiotherapy attains an almost 80% total survival rate. For patients with high grade sarcoma of >5 cm, local control can be attained by resection and radiotherapy, however every second patient will develop metastases. Patients with a local recurrence should consider a new resection. Radiotherapy is the more effective the lower the remaining postoperative tumor burden.     

Iridium-192 brachytherapy in the treatment of cancer of the prostate

Aggressive radiotherapy was used in 170 patients with advanced localized carcinoma of the prostate. After pelvic lymphadenectomy, 192Ir brachytherapy was used to deliver 3500 cGy to the prostate within 2 days. External-beam therapy (4500 cGy) was then given to a total of 8000 cGy. Random biopsies 18 months afterward were negative for residual cancer in 62 of 83 patients (75%), and 37 of 45 patients (82%) with pathologically proved localized disease remain without evidence of disease. Morbidity was significantly reduced in the most recent 70 patients by improvements in technique. The authors believe such therapy should be considered for patients with advanced stage B2 or C disease in particular.     

Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients

BACKGROUND: Despite three decades of debate, no conclusion has been reached concerning the effectiveness of postoperative radiotherapy for resected esophageal carcinoma. From 1986 through 1997, a prospective randomized study was carried out with 495 patients in an attempt to define the value of this therapeutic modality. METHODS: A total of 495 patients with esophageal cancer who had undergone radical resection were randomized by the envelope method into a surgery-alone group (S) of 275 patients and a surgery plus radiotherapy group (S + R) of 220 patients. Radiation treatment was started 3 to 4 weeks after the operation. The portals encompassed the entire mediastinum and bilateral supraclavicular areas. A midplane dose of 50 to 60 Gy in 25 to 30 fractions was delivered over 5 to 6 weeks. RESULTS: The overall 5-year survival rate was 31.7% for the S group and 41.3% (p = 0.4474) for the S + R group. The 5-year survival rates of patients who were lymph node positive were 14.7% and 29.2% (p = 0.0698), respectively. Five-year survival rates of stage III patients were 13.1% and 35.1% (p = 0.0027), respectively. CONCLUSIONS: Postoperative prophylactic radiotherapy improved the 5-year survival rate in esophageal cancer patients with positive lymph node metastases and in patients with stage III disease compared with similar patients who did not receive radiation therapy. These results were almost significant for patients with positive lymph node metastases and highly significant for patients with stage III disease.     

Repeat stereotactic radiosurgery for high-grade and large intracranial arteriovenous malformations

BACKGROUND: The treatment of large and high-grade (Spetzler-Martin III-V) AVMs remains a challenge. There is a paucity of literature addressing the efficacy of radiosurgery in this group. We retrospectively analyze our experience with repeat radiosurgery with such AVMs. METHODS: Between 1989 and 2004, 14 patients with large and high-grade AVMs deemed to be nonoperative candidates were treated with repeat radiosurgery. Patients were treated either on a LINAC or gamma knife-based system at 2- to 3-year intervals with targeting of the entire nidus with each treatment. Patients who did not receive their full treatment course or follow-up at the institution were excluded. RESULTS: Mean follow-up was 18 months. The complete obliteration rate was 35.7%, with a mean volume reduction of 53% in the remaining lesions. Twenty percent of grade III and 50% of grade IV lesions experienced cure. Complications included persistent headaches (2 patients). Statistical analysis revealed no difference between obliterated and partially obliterated groups with regard to mean pretreatment volume (24.87 cm(3)), median Spetzler-Martin grade (IV), mean follow-up (30.5 months), total delivered dose (3550 cGy), mean dose per stage (13 Gy), median number of stages (2), or mean interval between treatment stages (40 months). CONCLUSION: The present study demonstrates the potential role of repeat radiosurgery in the treatment of this cohort in the context of our short follow-up. The benefits of repeat therapy could be derived from using lower doses per session and repeat targeting of the lesion in an effort to increase response and decrease complication rates.     

Preoperative chemotherapy and radiotherapy for esophageal carcinoma.

From October 1986 to January 1991, 47 patients with esophageal cancer (29 squamous, 18 adenocarcinoma) were treated with simultaneous radiotherapy (3000 or 3600 cGy) and chemotherapy (infusional 5-fluorouracil, cisplatin) delivered during a 5-week period. This treatment was well tolerated; 44 patients (94%) completed a full course of therapy, 40 (85%) had relief from dysphagia, and 21 (45%) noted either weight gain or no net weight loss. One patient (2%) died of complications (tracheoesophageal fistula, perforated ulcer) during chemotherapy and radiotherapy. The remaining 46 patients were referred for operation. Six refused because of excellent relief of their dysphagia, and one was denied operation. Thirty-nine patients went to operation, and 34 (83%) had lesions that were resectable. Eight of the 39 surgically treated patients (21%) had no evidence of residual tumor identified in the resected specimens. One of these complete responders died 7 weeks postoperatively after multiple complications (3% operative mortality rate). Three of the remaining seven have also died since the operation, one of recurrent cancer and two with no known recurrent disease. Actuarial survival in this present series was significantly better than that of our 1980 to 1985 historical control patients (p less than 0.005). There was no difference between patients with squamous carcinoma and those with adenocarcinoma with regard to the prevalence of complete response or long-term survival. Survival of the seven patients who did not undergo operation was comparable with that of the 34 patients in whom esophagectomy was performed. This study suggests that combined preoperative chemotherapy plus radiotherapy for esophageal cancer is well tolerated, provides excellent palliation of symptoms, allows for a high rate of resectability, is equally effective for squamous carcinoma and adenocarcinoma, and provides encouraging early results with regard to long-term survival. The data also call into question the role of esophagectomy, particularly in patients who have a complete response to preoperative therapy.     

Endoscopic management of inoperable cholangiocarcinoma using iridium-192

We report a well tolerated endoscopic technique of administering intraluminal radiotherapy to 14 patients with inoperable cholangiocarcinoma, in which the iridium-192 wire source was inserted down a nasobiliary catheter placed within a previously inserted endoscopic biliary prosthesis, thus allowing bile flow to continue during treatment. Radiotherapy was commenced 2 weeks after biliary decompression, when the median serum bilirubin level had fallen from 213 to 34 mumol/l. A total radiation dose of 6000 cGy at 0.5 cm from the source was administered over a median of 85 h (range 77-116 h). In four patients there was a transient increase in serum bilirubin during iridium treatment and, in two cases (14 per cent), this was associated with mild cholangitis. Both cases resolved rapidly once the iridium wire and nasobiliary catheter were removed. The median hospital stay after treatment was 2.5 days (range 0-28 days). The late complications associated with stent blockage were minimized by routinely changing stents at 4-6 monthly intervals; ten of the patients have so far undergone from one to five (median three) stent changes. Five patients have died at 3.6-8.2 months (median 4.8 months) following iridium treatment; four had extensive type III hilar lesions at diagnosis. Nine patients are still alive at 5.4-31.0 months (median 16.4 months). The overall median survival after iridium therapy is 10.5 months. This technique of endoscopic biliary decompression before internal iridium administration minimizes complications by allowing biliary drainage during treatment. The role of this treatment in patients with inoperable cholangiocarcinoma awaits the results of randomized, controlled trials.     

Three decades of treatment of esophageal squamous carcinoma at the Massachusetts General Hospital

Seven hundred one patients with squamous cell carcinoma of the esophagus who were treated between 1950 and 1979 were retrospectively studied. The percentage of male patients decreased over the three decades (80% to 69%); the proportion of cigarette and alcohol abusers doubled. The esophageal carcinoma was located as follows: upper third, 24.7%; middle third, 52.8%, and lower third, 22.5%. There was disparity in clinical, surgical, and pathologic staging. More than two thirds of the patients thought to have stage II lesions preoperatively proved to have stage III lesions on pathologic examination; nearly one half of patients thought to have stage II disease intraoperatively were found to have pathologic stage III lesions. This "upgrading" of stage was chiefly a result of histologic recognition of nodal metastasis or extension of carcinoma into surrounding tissues. Operation was performed in 411 cases (58.6%) and resection was performed in 261 (37.2% overall). The postoperative death rate after resection fell from 30.5% in the 1950s to 10.4% in the 1970s, with respiratory complications the predominant cause of death. Analyses were based on treatment directed at the carcinoma itself: radiotherapy, 340 cases (48.5%); resection, 176 cases (25.1%); resection plus radiotherapy, 85 cases (12.1%); no definitive treatment, 100 cases (14.3%). Overall survival for the 701 patients was 13% at 2 years and 6% at 5 years (mean survival, 16.4 months); this did not differ by decade. Survival clearly differed by treatment (p = 0.001); resection plus radiotherapy provided the best survival (35% at 2 years; 20% at 5 years; mean of 32.5 months) followed by resection (18% at 2 years; 7% at 5 years; mean of 17.5 months), radiotherapy (9% at 2 years; 3% at 5 years; mean of 12.7 months), and no treatment (0% at 2 years; 0% at 5 years; mean of 2.5 months). Survival in patients who did not have resection did not differ by decade but survival in patients with resections improved in the last two decades. Patients with pathologic stage II lesions had greatly improved survival (54% at 2 years; 25% at 5 years; mean of 42.7 months) compared with patients with stage III disease (12% at 2 years; 6% at 5 years; (mean of 15.1 months) (p = 0.001).     

Photodynamic therapy of malignant brain tumours: a phase I/II trial

Twenty patients bearing malignant brain tumours (18 glioblastoma multiforme, one malignant meningioma, one melanoma metastasis) were treated 25 times with photodynamic therapy (PDT)--the combination of Hematoporophyrin derivative and light at 630 nm (40-120 J/cm2). Sixteen times the PDT was followed immediately by a single dose radiation of 4 Gy of fast electrons. Conventional radiotherapy following PDT was performed in eight patients. The median survival of three patients with multiple recurrences of glioblastoma grade IV and various chemo- and radiotherapy was 5 months. Four out of 10 patients with one recurrence and prior treatment died with a median survival of 5 months, six are still living up to 12 months. Six patients with a primary glioblastoma are surviving now up to 22 months. Phototoxicity to the skin, the only side effect of PDT, was noted in five cases, but did not pose any threat to the patients. The treatment did not affect the quality of life of the patients. Our preliminary results with the photodynamic treatment of malignant gliomas indicate that PDT might be a valuable addition to our armament in the treatment of such tumours.     

Radical prostatectomy after radiation therapy for cancer of the prostate: feasibility and prognosis

A total of 30 patients underwent an operation (radical prostatectomy in 27 and cystoprostatectomy in 3) for prostate cancer. In 17 patients radiotherapy with curative intent (range 5,700 to 7,500 cGy., mean 6,130 cGy.) had failed locally at 7 to 150 months (mean 48.8 months) later; 13 underwent the operation 2 months or less after planned radiotherapy (4,000 to 7,000 cGy., mean 5,431 cGy.). Followup was 1 to 16 years (mean 6.7 years). There was no perioperative death. The most significant complications were vesical neck contracture (17 per cent), lymphedema (10 per cent) and incontinence (10 per cent). Pathological staging revealed 8 patients with stage D1 disease. Of tumor grade, stage, adjuvant hormonal treatment and ploidy pattern only the last was associated with progression and survival. An increasing number of patients with local, albeit often symptomatic, radiation failure may present during the next years and they must be treated. Salvage prostatectomy is feasible and its associated morbidity seems to be acceptable; alternative (nonoperative) treatment modalities have proved not to be effective. Deoxyribonucleic acid ploidy pattern can provide valuable prognostic information in this difficult patient population for decision-making regarding radical surgery and adjuvant hormonal treatment.     

Preoperative radiotherapy in the treatment of soft tissue sarcomas

The goal of the current study was to analyze the oncologic results and wound complications in patients with soft tissue sarcomas treated with preoperative radiation therapy and en bloc resection. A standard protocol of preoperative radiotherapy was administered followed by en bloc resection in 209 patients. The protocol included needle or incisional biopsy, prospective staging, a consistent dose of radiotherapy, standardized prospective evaluation of surgical margins, and long-term followup. The target radiotherapy dose was 50.4 cGy. Twenty-nine patients had low-grade lesions, and 180 had high-grade lesions. The mean followup was 55 months. The significant wound complication rate was 22% (moderate 14%, major 7%, and amputation 1%). Wound complications were significantly higher in patients with lower extremity lesions when compared with patients with upper extremity or axial lesions, and in patients with lesions larger than 5 cm. The local recurrence rate was 11% in patients who did not have prior surgery, and 37% in patients who had prior surgery at an outside institution (17% overall). Local recurrence was increased significantly in patients who had prior surgery. At latest followup, 78 patients (47%) were continuously disease-free, six (4%) were alive with no evidence of disease, nine (5%) were alive with disease, 63 (38%) died of disease, and 11 (7%) died of another cause. The 2- and 5-year disease-specific survival rates were 77% and 67%, respectively. Overall survival was 56%. A significant decrease in survival was seen in patients who had a local recurrence, and in patients with high-grade lesions. Preoperative radiotherapy can be given safely with a wound complication rate not significantly higher than that reported for other forms of radiotherapy delivery. Local recurrence tends to be higher if surgical intervention is done before tertiary center referral. Distant disease continues to be the cause of the high mortality in these patients.     

Treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy.

Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluouracil and cisplatin and 30-36 Gy of radiation to determine whether these tumours are responsive to such treatment. Complete regression of tumour was observed endoscopically in 19 patients, and partial regression in four. Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen. Nine patients received additional radiotherapy to a total dose of 54-60 Gy instead of surgery. Tumour response was associated with rapid reversal of dysphagia. Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture. Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy, and a tumour of less than 5 cm in length. The median survival of responding patients was 15 months. Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation.     

Sphincter-Preserving Operations Following Preoperative Chemoradiation: An Alternative to Abdominoperineal Resection for Lower Rectal Cancer?

BACKGROUND: Sphincter-preserving operations (SPO) for lower rectal cancer are on the rise. In the study reported here, we compared the oncologic outcomes of patients who underwent sphincter-preserving operations following preoperative chemoradiation for lower rectal cancer with the outcome for patients who underwent abdominoperineal resection (APR). METHODS: This prospective study included 87 patients who underwent proctectomy with curative intent for locally advanced rectal cancer that was located less than 6 cm from the anal verge. Forty-four patients had APR with no preoperative treatment. Forty-three patients underwent concurrent chemoradiation therapy (CCRT) consisting of preoperative 5-fluorouracil-based chemotherapy and pelvic radiation (4500-5040 cGy); this was followed 6 weeks later by surgery (SPO/CCRT). The oncologic outcomes between the two groups were compared, and factors affecting survival were evaluated. RESULTS: The median follow-up period was 56.2 months. The overall postoperative complication rates did not significantly differ between SPO/CCRT and APR (32.6% versus 34.2%; p = 0.879). Also, there were no significant differences in the overall recurrence rate (20.9% versus 20.5%; p = 0.956) and 5-year overall survival rate (70.8% versus 62.9%; p = 0.189) between the two groups. By multivariate analysis, only the pathologic N stage was significantly associated with overall survival (p < 0.001). CONCLUSIONS: Sphincter-preserving operation with CCRT could be another option for the treatment of locally advanced lower rectal cancer in patients who are clinically considered for APR, with no deterioration of oncologic outcomes. For patients undergoing curative resection for lower rectal cancer, the pathologic N stage can provide valuable prognostic information about survival.     

Resection of advanced cervical metastasis prior to definitive radiotherapy for primary squamous carcinomas of the upper aerodigestive tract.

Thirty-five previously untreated patients with stage IV squamous cell carcinoma of the upper aerodigestive tract with advanced neck disease (mass greater than 3 cm) but with primary lesions thought to be locally controllable with radiotherapy were selected between 1972 and 1988 for treatment by neck dissection followed by radiotherapy; postoperative to the neck and definitive to the primary. Limited neck dissections spared muscles, nerves, and vasculature structures unless clinically involved with cancer. All patients received at least 50 Gy, postoperatively, to the entire neck with doses of up to 75 Gy being delivered to the primary treatment portals. Regional (neck) failure occurred in 11% (4 of 35) patients. Overall, 5-year survival from cancer was 55%. Multiple levels of neck involvement were associated with poorer survival than a single large node; however, the difference was not statistically significant. Delay in the institution of radiotherapy following surgery adversely affected survival (p = 0.01). This study demonstrates that in selected patients it is possible to resect advanced nodal metastasis prior to treating the primary with radiotherapy without compromising cancer control.     

Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum.

OBJECTIVE: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. SUMMARY BACKGROUND DATA: The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. METHODS: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. RESULTS: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients. CONCLUSIONS: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.