Neelofur Ahmad

Palliative reirradiation for recurrent rectal cancer

PURPOSE The purpose of this study was to analyze the efficacy and acute and late toxicity of reirradiation for recurrent rectal cancer. METHODS AND MATERIALS Fifty-two patients with recurrent rectal adenocarcinoma following previous pelvic RT underwent reirradiation. Median initial RT dose to the pelvis was 50.4 Gy. Median reirradiation dose was 30.6 Gy. Twenty-two patients received 1.2 Gy b.i.d., and 30 patients received 1.8-2.0 Gy daily. Total cumulative doses ranged from 66.6 to 104.9 Gy (median: 84.4 Gy). Forty-seven patients (90%) received concurrent 5-FU chemotherapy. Forty-four patients were followed until death, and the median follow-up time was 16 months. RESULTS The RTOG Grade 3 acute toxicity rate was 31%. The RTOG Grade 3 and 4 late toxicity rates were 23 and 10%, respectively. On multivariate analysis, the only factor associated with reduced late toxicity was hyperfractionated delivery of reirradiation. Bleeding, pain, and mass effect were palliated completely in 100, 65, and 24% of instances, respectively, and the majority of responding patients were palliated until death. The overall median survival time from retreatment was 12 months. The 2- and 3-year overall actuarial survival rates were 25 and 14%, respectively. CONCLUSION This unique institutional approach to recurrent rectal cancers resulted in excellent palliation of symptoms. Late complications appeared reduced by hyperfractionated treatment delivery.

Combined liver radiation and chemotherapy for palliation of hepatic metastases from colorectal cancer.

PURPOSE To report the effects of boost dose radiation on palliation, survival, and toxicity in patients undergoing palliative treatment for hepatic metastases from colorectal cancers and to assess the potential benefits of higher doses of radiation to partial liver volumes. MATERIALS AND METHODS Forty-five patients with hepatic metastases from colorectal cancers were treated with a course of palliative irradiation. Eligible patients included those with radiographically or histologically proven liver metastases. All patients but one received chemotherapy, either pretreatment (one patient) and/or concurrently with radiation (43 patients) via intravenous or hepatic intraarterial infusion. Patients were divided into two groups based on whether or not boost radiation was given. Thirty-three of the 45 patients (group 1) received whole-liver irradiation at doses that ranged from 8 to 31 Gy at 2.0 to 3.0 Gy per fraction (median dose, 21 Gy). The remaining 12 patients (group 2) received liver irradiation to 20 to 30 Gy followed by a boost dose to the area of dominant disease for a total dose of 33 to 60 Gy. The extent of liver involvement was similar between the two groups. Palliation, overall survival, and toxicity were analyzed with respect to radiation dose. RESULTS There was no increase in acute effects observed in treating partial liver volumes to higher doses in conjunction with systemic chemotherapy. No cases of radiation-induced hepatitis or nephritis were documented. Hematologic toxicity (> or = grade 3) was observed in four patients with thrombocytopenia, three with leukopenia, and two with anemia. Pain was relieved in 71% and hepatomegaly in 59% of group 1 patients, as compared with 100% and 89%, respectively, of group 2 patients. Other symptoms such as nausea, fever, fatigue, and jaundice were palliated in 35% of group 1 and 90% of group 2 patients. The median survival time for group 1 patients was 4 months (range, 1 week to 26 months), which is consistent with that reported in the literature. The median survival time for group 2 patients was 14 months (range, 2 to 32 months) (P=.01). CONCLUSION Standard hepatic irradiation followed by boost radiation to partial liver volumes in combination with chemotherapy is well tolerated without significant acute/late morbidity. Higher radiation doses to partial liver volumes offers improved palliative benefit and may prolong survival without an increase in morbidity.

High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

PURPOSE A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. METHODS AND MATERIALS Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy, +/- 10% (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers (fixed, low-lying, or deeply ulcerated) were given a higher dose, 55 Gy, +/- 10%, using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. RESULTS Fourteen percent (38/275) of the total group developed a local recurrence; 20% (31/156) in the low-dose group as compared with 6% (7/119) in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. CONCLUSION High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. However, in clinically unfavorable cancers a higher dose (55 Gy) of preoperative radiation can be given safely with significantly improved local control. Careful clinical staging is helpful in selectively treating patients with unfavorable tumors to a higher preoperative radiation dose and thus optimizing their outcome.

A selective approach to adjunctive therapy for cancer of the rectum

PURPOSE To present results of a selective approach to adjunctive therapy and surgery based on a new model of clinical staging for rectal cancer. METHODS AND MATERIALS Three hundred and sixty-two patients with rectal cancer treated with adjunctive radiation therapy and surgery have been analyzed to define patient selection criteria based on clinical assessment of disease. Clinical prognostic features of tumor mobility and level of lesion in the rectum with reference to the anorectal junction were used. Mobile, early fixed (partial), advanced fixed (total) and frozen pelvis are defined as clinical Stages I, II, III, and IV. Tumors above 6 cm (middle valve), 3-6 cm (inferior to middle valve), 0-3 cm (anorectum to inferior valve), and into the anal canal are defined as levels a, b, c, d, respectively. Based on this model, patients with mobile tumors of the proximal rectum (CS Ia, b) are treated with 500 cGy preoperative radiation and selective postoperative radiation (4500 cGy) for Stages B2 and C cancer. All other patients are treated with escalating doses of preoperative radiation. Follow-up in these patients ranges from 1 year to 14 years with a median of 5 years. RESULTS Overall 5-year survival of the total group of patients is 69%. Survival by pathological stage is 82% for O, A, B1, 67% for B2, 74% for C1, and 51% for C2. Survival by clinical stages is 77% for CS I, 67% for CS II, 57% for CS III, and 21% for CS IV. Overall local recurrence is 43/362 (12%). L.R. by pathological stages is 5% for O, A, B1, 18% for B2, 10% for C1, and 17% for C2. L.R. by clinical stages is 9% for CS I, 14% for CS II, 17% for CS III, and 50% for CS IV. CONCLUSION An integrated adjunctive therapy and selective surgical approach based on careful clinical staging of rectal cancer results in a global improvement in overall local control and survival of patients.

PRE-OPERATIVE CHEMORADIATION FOR ADVANCED RECTAL CANCER

Radical surgery remains the primary treatment for most carcinomas of the rectum. However, high local recurrence rates following surgery alone have prompted the investigation of a variety of adjuvant treatments. These have included preoperative and/or postoperative radiation therapy, chemotherapy, and combinations of radiation and chemotherapy (1, 4, 6, 7, 9, 12-16). The series of patients treated with combined preoperative radiation and chemotherapy presented by Chan et al. (2) in this issue highlights several significant aspects of preoperative radiation therapy in this disease. Perhaps most important is the recognition that rectal cancer represents a broad spectrum of disease requiring tailored treatment regimens to maximize outcome. Chan et al. (2) focused their preoperative chemoradiation protocol on patients with “tethered or fixed” rectal cancers, acknowledging the negative prognostic impact of tumor fixation preoperatively (15). Rather than classifying all of the patients into a single “unfavorable” or “unresectable” group, the authors used specific criteria for tethering and fixation in the pretreatment evaluation of their patients. This allowed subsequent meaningful comparison of the outcome of the group by tumor mobility. Additionally, this facilitates comparisons between their series and others using similar criteria ( 10, 11, 15, 17).

Differential dose delivery using a nondocking applicator for intraoperative radiation therapy

PURPOSE Although treatment of a field within a field to deliver a boost dose is quite common with external photon beam radiation therapy, the same is not always true with electron beam radiation or in intraoperative radiation therapy (IORT). The purpose of this work is to report the results and details of a new technique developed to treat a field within a field in intraoperative radiation therapy. METHODS AND MATERIALS This technique makes use of the nondocking IORT system currently used at our institution. Treatment is given in two segments: the large field is first treated by using standard circular lucite cones; the second dose segment is delivered using a new circular brass cone designed to fit concentrically within the large lucite cone. RESULTS Central axis depth dose, surface dose, output factors, and two-dimensional beam profiles have been measured for a 7 cm inner diameter (i.d.) flat lucite cone and 3.8 and 5 cm i.d. flat brass cones for electron beam energies ranging from 4-22 MeV. For different clinical target volumes, summed dose distributions differentially weighted in both energy and dose are presented. CONCLUSIONS A simple technique for delivering differential dose in intraoperative radiation therapy is presented. The technique provides a method for escalating dose to higher values for a defined target volume.