Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.     

Preoperative combined modality treatment for rectal cancer

The encouraging results achieved with adjuvant postoperative combined modality therapy in patients with resectable rectal cancer has prompted an increased interest in preoperative combined modality therapy. Based on the potential of such regimens to deliver higher chemotherapy doses, enhance downstaging, and decrease acute toxicity in patients with unresectable disease, this approach is attractive in patients with resectable rectal cancer. Randomized trials of preoperative vs postoperative combined modality therapy using combinations of bolus fluorouracil and leucovorin are in progress.     

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.     

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593

PURPOSE: To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia

The standard modality of the treatment for the patients with T4 esophageal cancer, whose prognosis still remains quite poor, is not established yet. Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemo-radiotherapy has become to be available. During the period from 1992 to 96, 30 patients with the suspected T4 esophageal cancer underwent chemoradiotherapy, which consisted of two courses of CDDP/5-FU with-sequential or concurrent 50-60Gy radiotherapy. Among them eleven patients became to be resectable by means of thoracotomy and laparotomy and pathological CRs were obtained in either primary lesions or lymph nodes. The longest survival term following surgery is 36 months. Three patients died of cancer recurrence including the organ metastasis and one died from pyothorax without cancer due to severe immunosuppression attributable to chemoradiation. Our results warrants further studies of neoadjuvant chemoradiotherapy for the patients with T4 esophageal cancer.     

Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT

OBJECTIVE: This study was conducted to determine the criteria for unresectability of major peripancreatic vessels in patients with pancreatic carcinoma as revealed by optimally enhanced, pancreatic-phase thin-section helical CT. SUBJECTS AND METHODS: Twenty-five patients with pancreatic adenocarcinoma who underwent local dissection during curative or palliative surgery also underwent preoperative pancreatic-phase thin-section helical CT (40- to 70-sec delay, 2.5- to 3-mm collimation). Tumor involvement of the portal and superior mesenteric veins and the celiac, hepatic, and superior mesenteric arteries was prospectively graded on a 0-4 scale based on circumferential contiguity of tumor to vessel. Subsequent surgical results were then correlated with the CT grades. RESULTS: At surgery, definitive evaluation was possible for 80 vessels. Forty-eight of 48 vessels graded 0 and three of three vessels graded 1 were resectable. Four of seven vessels graded 2, seven of eight vessels graded 3, and 14 of 14 vessels graded 4 were unresectable. A threshold of between grades 2 and 3, which corresponded to tumor involvement of one-half circumference of the vessel, yielded the lowest number of false-negatives and an acceptable number of false-positives for unresectability. Such a threshold would have yielded a sensitivity of 84%, a specificity of 98%, a positive predictive value of 95%, and a negative predictive value of 93% for unresectability of the vessels studied. CONCLUSION: A grading system for tumor involvement of the major vessels in patients with pancreatic adenocarcinoma can be based on the degree of circumferential contiguity of tumor to vessel. Involvement of vessel to tumor that exceeds one-half circumference of the vessel is highly specific for unresectable tumor.     

Phase II study on preoperative radio-chemo-thermotherapy in locally advanced rectal carcinoma

BACKGROUND: Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas. PATIENTS AND METHODS: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. RESULTS: Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too. CONCLUSIONS: Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.     

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06

PURPOSE: Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. PATIENTS AND METHODS: Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] < 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total 69.6 Gy). RESULTS: Seventy-six assessable patients with a Karnofsky performance status > or = 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of < or = 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). CONCLUSION: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.     

Carcinoembryonic antigen induces signal transduction in Kupffer cells

OBJECTIVES: We compared the ability of preoperative abdominal computed tomography (CT) with that of preoperative abdominal ultrasonography (US) in predicting the extent of tumor growth and the curative resectability of gastric cancer. METHODS: Abdominal CT and US were done in 95 patients with gastric adeno-carcinoma. The radiologic findings were prospectively compared with surgical and pathologic findings. RESULTS: The sensitivities of abdominal CT and US in detecting the perigastric lymph node involvement were 26.6% and 20%, respectively. The sensitivity of abdominal CT in predicting the pancreatic invasion (60%) was better than that of abdominal US (20%). However, there were 6 false positive diagnosis of pancreatic invasion by abdominal CT; in contrast, there was no false positive diagnosis of pancreatic invasion by abdominal US. Of 95 patients who underwent surgical exploration, 14 were found to have unresectable tumors because of extragastric organ involvement and distant metastases. Abdominal CT falsely predicted 8 of 14 cases in which curative gastric resection was impossible as resectable. Moreover, abdominal CT falsely predicted 5 of 81 cases in which curative gastric resection was possible as unresectable. Abdominal US falsely predicted 12 of 14 cases in which curative surgery was impossible as resectable. CONCLUSION: Preoperative abdominal Ct and US did not accurately predict the tumor extent and the curative resectability of the gastric cancer. Especially, abdominal CT finding of pancreatic invasion by gastric cancer should not be a contraindication for surgical exploration.     

What do we really know about Helicobacter pylori in gastric ulcer disease?

Advances in diagnostic and therapeutic technology have not appreciably changed the outlook of patients with pancreatic cancer. While those patients presenting with localized resectable disease have the best prognosis, local control and intra-abdominal metastases remain significant obstacles to survival. Localized chemoradiation has modestly improved median survival in localized and locally advanced disease. Patients presenting with locally advanced disease at diagnosis benefit from surgical palliation which includes biliary and gastric bypass. Intraoperative interstitial brachytherapy has been effective when utilized at laparotomy to improve local control in locally advanced disease. Advances in laparoscopic techniques have provided the ability to more accurately stage patients prior to laparotomy and perform palliative procedures without the need for laparotomy. The utilization of high-dose-rate brachytherapy has proven effective in palliating obstructive symptoms with minimal morbidity on an outpatient basis. Recent efforts have focused on preoperative chemoradiation to improve resectability in selected patients and prophylactic hepatic irradiation to reduce metastases for patients with locally advanced disease.     

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer

BACKGROUND: This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS: Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS: We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).     

Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival

PURPOSE: To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented. PATIENTS AND METHODS: Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy. RESULTS: Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis. CONCLUSION: PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.     

Studies on the phototoxic effects of oral antidiabetics and diuretics

Combined chemoradiotherapy (CT/RT) treatments appear to yield better results for advanced tumours of the head and neck than do conventional therapies. In the present study, CT/RT was used preoperatively in unresectable tumors of the oral cavity and oropharynx. Forty patients were entered prospectively into a phase II study. Treatment consisted of three cycles of chemotherapy with cisplatin and 5-day infusion of fluorouracil (FU), and the addition of simultaneous radiotherapy (30 Gy) from the second to third cycles. Patients with resectable residual disease or complete clinical response underwent surgery. All patients later received a second phase of irradiation (30 Gy) and two cycles of chemotherapy only in responders. During the first phase of treatment, 22 (55%) patients presented mucositis grades III-IV. Mean weight loss was 7%. Twelve patients were admitted for parenteral nutrition. Thirty-six (90%) patients obtained clinical response, which was complete in 15 (37%). Thirty-two of the 40 underwent surgery. The percentage of pathologic complete responses (PCR) was 35% (14 patients). With a median follow-up of 21 months, the median survival of patients was 23 months, and 19 (47%) of them are disease-free. A high PCR rate was attained with this treatment regimen. Toxicity was significant, but tolerable with adequate support measures.     

Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

INTRODUCTION: Improvements of the results of combined chemoradiotherapy (CRT) in esophageal cancer has led several groups to adopt a non surgical attitude specially in case of complete response (endoscopy +/- biopsy). Few information are available about the follow-up of these patients. We studied long-term results of 35 patients who underwent resection after complete response to preoperative chemoradiotherapy. PATIENTS AND METHODS: 161 patients with resecable carcinoma of the thoracic esophagus have received the same protocol of CRT (cisplatin 80 mg/m2, radiation therapy split course: 37.5 Gy) all patients were followed every for 4 months (no lost of view). RESULTS: Complete response (endoscopy and biopsy) was obtained for 35 patients (21.7%), 19 of them (54%) had pathologic complete response (PCR) (no tumor in the specimen), 16 have microscopic foci of residual tumor (46%). The overall 5-year survival rate was 49.8% for the whole group (median survival 64 months), 70% for the group without tumor in the specimen, 48% for the group with microscopic foci of residual tumor (NS). CONCLUSIONS: One half of the complete response (endoscopy + biopsy) have not a pathologic complete response (microscopic foci of residual tumor in the specimen). The 49.8% of five year survival suggests a benefit from esophagectomy for complete response after combined chemoradiotherapy.     

Exfoliative cytology for diagnosis of Helicobacter pylori]

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.     

Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.     

Pancreatic duct stricture length at ERCP predicts tumor size and pathological stage of pancreatic cancer

OBJECTIVE: To determine whether findings on endoscopic retrograde cholangiopancreatography (ERCP) could provide useful prognostic information in resectable pancreatic cancer. METHODS: We retrospectively identified 18 patients with resectable pancreatic cancer (defined as no evidence of metastatic disease or vascular involvement on CT scan) who had undergone ERCP prior to an attempt at curative resection between 1991 and 1996. Common bile duct and pancreatic duct stricture lengths were measured on ERCP and compared with the size of the resected tumor. Magnification was controlled for by comparison with endoscope diameter. Stricture length was plotted against actual tumor size, and a correlation analysis was performed. RESULTS: Pancreatic duct stricture length measured on ERCP correlated with both size (p < 0.001) and stage (p < 0.002) in resectable pancreatic cancer. CONCLUSIONS: ERCP may provide useful preoperative prognostic as well as diagnostic information in pancreatic cancer.     

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.