Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. First-year quality of life assessment of an intra-arterial (RADPLAT) versus intravenous chemoradiation phase III trial. Conventional approach x laparoscopic abdominoperineal resection for rectal cancer treatment after neoadjuvant chemoradiation: results of a prospective randomized trial. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Role of chemoradiation in advanced cervical cancer. Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma. Bioresorbable hyaluronate-carboxymethylcellulose membrane (Seprafilm) in surgery for rectal carcinoma: a prospective randomized clinical trial. [The effects of thymostimulin in a protocol of concurrent hyperfractionated carboplatin and irradiation]. Desmoplastic small round cell tumor in children: a new therapeutic approach.
The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation.
                Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery.
                Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response.
                Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders. Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups.
                The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months.
                Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively.
                Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone. A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone.
                One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42.
                At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power.
                This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference. We report the results of a multicenter randomized phase III study, assessing quality of life (QOL) in intra-arterial (IA) versus standard intravenous (IV) chemoradiation in advanced head and neck cancer.
                Two hundred seven patients with inoperable stage IV disease-152 men and 55 women; mean age, 55 years-were included in this study. The patients were treated with standard radiotherapy with 4 weekly IA or 3 weekly IV cisplatin infusions. The QOL assessments carried out were EORTC-C30, H&N35, and trial-specific questionnaires.
                Overall QOL deteriorated in all patients during treatment, is gradually improving over 1 year. IA patients showed significantly less nausea and vomiting at week 7 (p <.001). IV patients were significantly more fatigued (p <.006). At 1 year, no significant difference in tube feeding was found. Voice quality slightly exceeded the pretreatment values at 1 year. Forty-two of 62 employed patients returned to work.
                During treatment, significantly fewer problems with nausea and vomiting occurred in IA than in IV patients. Both groups showed improved voicing and oral intake during follow-up, often exceeding pretreatment values at 1 year.
                (c) 2008 Wiley Periodicals, Inc. Head Neck, 2009. The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation.
                Twenty eight patients with distal rectal adenocarcinoma were randomized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospectively. Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach.
                There was no significant difference (p<0,05) between the two studied groups regarding: gender, age, body mass index, patients with previous abdominal surgeries, intra and post operative complications, need for blood transfusion, hospital stay after surgery, length of resected segment and pathological staging. Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach (p=0.04). Mean anesthesia duration was shorter (p=0.03) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes, respectively. There was no need for conversion to open approach in this series. After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery, local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group.
                We conclude that laparoscopic abdominoperineal resection is feasible, similar to conventional approach concerning surgery duration, intra operative morbidity, blood requirements and post operative morbidity. Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer. Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy.
                The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat.
                Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up.
                Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made. A prospective randomized study was conducted in our department of Radiotherapy, Regional Institute of Medical Sciences, Imphal to evaluating the role of chemoradiation in the management of advanced inoperable cervical cancer (stage IIB-IIIB) taking only radiation treatment as control spanning the period 1996-1999. Of the fifty patients accumulated in the study group, three patients did not complete treatment, one expired due to other causes and three were lost to follow up. Likewise, of the forty-six patients in the control group, one patient did not complete treatment and 4 were lost to follow up. Thus only 43 and 41 patients were available for the result analysis for the study and control groups respectively. The early treatment response as assessed after two months of treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete response (CR), partial response (PR), and total response (TR) respectively for the study and control groups. Our patients included in this study had a median follow up of 35 months and 33 months for study and control groups respectively. For this follow up, the disease-free survival, survival with disease and overall survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control groups respectively. There was an increase in early side-effects in the chemoradiation group but the difference was not significant. Because of the early side effects, treatment delays ensued in 7 patients (16.3%) and in 3 patients (7.3%) in the study and control groups respectively. There was no significant increase in the late treatment toxicities in both the groups. To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer.
                Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months).
                Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT.
                Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients. To evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy.
                A total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA-). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome.
                Seprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates.
                Seprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery. To evaluate the effect of thymostimulin in a treatment schedule of concurrent hyperfractionated chemoradiation therapy, with the cytostatic forming part of each therapeutic fraction, the authors included in this protocol 36 patients with advanced head and neck carcinomas randomized into two groups. Group A received 115 cGy + 5 mg/m2 of carboplatin per fraction in two daily fractions for a total dose of 8.050 cGy + 700 mg of carboplatin, while group B received the same treatment associated with thymostimulin, with the following schedule: 1.5 mg/kg/day in the week before chemoradiation + 1.5 mg/kg twice a week during treatment + 1 mg/kg twice a week for two years or until recurrence. The results were evaluated upon reaching 18 months of follow-up (30 maximum). A smaller decrease in lymphocyte levels was observed in group B, but no differences were seen in toxicity between the groups. Patients included in the B group had a slightly longer disease-free-survival interval, but 17% of recurrences and 11% of distant metastases were observed in the A group, whereas 22% of recurrences and 22% of distant metastases were seen in the B group. The number of complete remissions (94%) was the same in both groups. Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histologic and immunohistochemical features occurring in a young population with a male predominance. The tumor appears to arise as masses in the abdominal cavity without a clear visceral origin. Five patients with DSRCT were treated as usual with combined chemoradiation and surgery. In addition, in our center, patients underwent autologous bone marrow transplant (BMT), which is a novel approach to this disease.
                Charts of 5 patients (4 males, mean age of 11 years) treated between 2000 and 2007 were reviewed. The diagnosis of DSRCT was made on the basis of clinical examination, computed tomographic scan, and explorative laparotomy with biopsy, and biochemical markers were negative. All patients were treated with aggressive chemoradiation and surgery. Three patients also had autologous BMT.
                Three patients (BMT recipients) responded to treatment. The responding patients had surgery with the intent of removing all disease. Two patients died of their cancer, neither of whom underwent BMT.
                The patients DSRCT are sensitive to an aggressive combination of chemotherapy, surgical debulking, and radiation therapy, followed by autologous BMT. It appears that this new multifaceted treatment offers good palliation, which may prolong survival and a possible cure.
Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.