Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group.

Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone. Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months). This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed.

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation.

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314.

Following documented evidence of the synergism of 5-fluorouracil (5-FU) and radiation therapy and an additive effect with mitomycin and irradiation, pilot studies have demonstrated the potential for definitive radiation therapy in the management of squamous cell and basaloid carcinomas of the anal canal, allowing sphincter preservation. Our study explored the long-term effectiveness of combined therapy at this disease site and examined the feasibility of a Radiation Therapy Oncology Group study involving concomitant radiation therapy and chemotherapy. Between 1983 and 1987, 79 assessable patients with any primary tumor stage of anal canal carcinoma were treated by external-beam irradiation combined with mitomycin given by bolus iv injection and 5-FU given by continuous infusion. Radiation was delivered to the perineum and pelvis to a total dose of 4,080 cGy in 4.5-5 weeks. The inguinal nodal areas received 4,080 cGy, calculated at a 3-cm depth in the center of the nodal area. A 96-hour infusion of 5-FU was started on days 2 and 28 of the irradiation at a dose of 1,000 mg/m2 over 24 hours, and a bolus injection of mitomycin was administered on day 2 at a dose of 10 mg/m2. The overall survival rates are 97% at 1 year and 73% at 3 years. Patients with lesions less than 3 cm in diameter and those treated strictly according to the protocol did significantly better than those with larger lesions and those whose treatment did not comply with the protocol. The interim outcome of the study demonstrates that this combined therapy is effective for patients with anal cancer and allows preservation of the sphincter and of sexual function.

Definitive radiation therapy for selected cancers of the rectum.

During the last 15 years, over 400 patients with adenocarcinoma of the rectum have undergone a course of endocavitary irradiation for cure or palliation of Dukes' A and B disease. This treatment method makes use of an unconventional fractionation scheme, by which the tumour receives 10,000-12,000 cGy in approximately four fractions over a period of about 60 days. The treatments are separated by an interval of 2 or 3 weeks. This method of definitive irradiation allows suitable patients to avoid abdominoperineal resection and its drawbacks. Hospitalization is avoided and the patients maintain a normal daily life. Approximately 15-20 per cent of all rectal cancer patients may be expected to fulfil the criteria for selection, which are sufficiently strict that the local control (95 per cent) and 5-year survival rates (94 per cent) can exceed those of surgery for comparable disease.

Combined modality preoperative therapy in poor prognostic rectal adenocarcinoma.

Between 1976 and 1986, 64 patients with rectal adenocarcinoma who were considered unresectable or had prognostic signs suggestive of high risk for local failure received preoperative adjuvant therapy. They were treated with pelvic irradiation (40 Gy) combined with 5-fluorouracil (5-FU) and mitomycin-C, followed by surgery. All had definitive resections resulting in 12.5% of operative specimens free of tumor and only 26.5% containing nodal metastases. The projected 5-year disease-free survival rate is 64% with an actuarial survival of 68%. No mortality or severe morbidity has been observed. Combined modality therapy is a safe and effective regimen for those rectal tumors in the high risk category.

Treatment of breast cancer among elderly women with segmental mastectomy or segmental mastectomy plus postoperative radiotherapy.

Elderly women with cancer are often treated non-aggressively. Between January 1972 and March 1984, 128 women greater than 60 years were treated for Stage I or II breast cancer with segmental mastectomy (SGM) plus/minus postoperative radiation at one of our four area hospitals. Whereas 82% of similar patients less than 60 years were referred for postop radiation, only 39.8% of patients greater than 60 were so referred. Referral rates progressively diminished with increasing patient age above 60. Thus, we reviewed the outcome of 77 elderly women treated with SGM and 51 treated with SGM+RT. Treatment groups were similar with regard to prognostic clinical and histologic parameters. Mean follow-up is 51.4 months. Among SGM patients, 45.5% of patients between 60-70 years, 37.9% of those greater than 70, and 20% of those greater than 80 years experienced loco/regional failure prior to death. Conversely, only two local failures occurred among all elderly women treated with SGM+RT. Distant failure was approximately 11% and was unaffected by treatment. Complications of SGM+RT were modest. These data suggest that SGM+RT can be safely and effectively applied to the elderly. Moreover, the data suggests that postop radiation may be more beneficial when extended to elderly patients post segmental mastectomy than among younger women. Referring surgeons should focus upon their patients' physiologic and not chronologic age as a basis for treatment allocation decisions.

Squamous cell carcinoma antigen as a marker for squamous cell carcinoma of the anal canal.

Twenty-one patients with documented squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 101 serum samples for radioimmunoassay of SCC antigen to evaluate regression or progression of disease. Eighteen presented with primary SCC of the anal canal, two with metastatic disease, and one with a recurrence in the perineum. Median follow-up was 18 months. Thirteen of 22 serum samples were true-positives, and nine of 22 were false-negatives. Four of 79 serum samples were false-positives and 75 of 79 were true-negatives. The sensitivity of this test is 59% and the specificity is 95%, with the accuracy of a positive test being 76%.

Dosimetry of an endocavitory treatment system.

The dosimetric properties of an x-ray applicator system for the treatment of rectal carcinoma by endocavitory contact therapy are discussed. Half-value layer, percent depth dose, field flatness, and output dose rate were evaluated. Film was used to evaluate field flatness and ionization chambers were used to evaluate the other quantities. The methods of measurement and their results are discussed.

CT staging of early rectal carcinoma.

Of 43 rectal carcinomas, initially presumed to be modified Dukes' stage A or B-1, 42 were examined with computed tomography (CT) prior to endocavitary treatment or surgery in 40 cases. The CT correctly showed 28 patients to have early stages and incorrectly showed 2 to have perirectal extension. Three patients had anal neoplasms. The remaining 10 patients had disease stage B-2 or higher and CT was not good for staging them. A CT scan can fairly accurately stage rectal carcinomas stage A and B-1 grouped together, and is doing better in predicting the prognosis than digital palpation when histologic sections show well or moderately well-differentiated adenocarcinoma of the rectum.

Intraoperative electron beam radiation therapy with particular reference to the treatment of rectal carcinomas--primary and recurrent.

Radiation therapy is being used alone or in combination with surgery with increasing frequency in the treatment of colorectal malignancies. Preoperative or postoperative irradiation may be offered to patients with marginally resectable lesions who are at high risk for local recurrence. Dose levels required for cure, however, may be such that the complications are unacceptable. The use of intraoperative radiation therapy (IORT) has increased the possibility of a higher local control rate and possible cure. The ability to increase the therapeutic ratio between local control and complications using IORT is achieved only with close interaction between the surgeon and radiation oncologist. Furthermore, intraoperative radiation therapy may be offered for patients with recurrent rectal tumors. The technique of intraoperative radiation therapy will be described briefly and recent results regarding colorectal cancers from larger centers will be reviewed. It appears from many reports that the three-to-five-year results for marginally resectable disease are approximately 50 percent and for recurrent disease, approximately 40 percent. The incidence of complications following intraoperative radiation therapy does not appear to increase as a result of this aggressive treatment modality. The number of centers offering this modality is increasing rapidly.

The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum.

For many years surgery has been the treatment of choice for squamous cell carcinoma of the anus, but it is now becoming apparent that well-planned definitive radiation therapy combined with chemotherapy may obviate the need for an abdomino-perineal resection. Since 1976, 33 patients with this disease were treated at Highland Hospital by radiation therapy combined with 5-FU and Mitomycin-C for sensitization. Four of these patients underwent a planned abdomino-perineal resection following therapy; the operative specimens of all four patients were negative for tumor. Twenty-nine patients were treated by the above method without surgery in a definitive manner and local control was achieved in 89.6% of patients. Radiation therapy combined with 5-FU and Mitomycin-C for sensitization has also been used in an effort to improve the resectability rate of large rectal cancers and ultimately the 5-year survival of patients with this disease. Fifty-eight patients with marginally resectable carcinoma of the rectum were treated pre-operatively by this regimen. The method of administration of the chemotherapeutic agents used for sensitization appears to be an important factor in obtaining an increased therapeutic ratio. Thirty-three patients have been followed for a minimum of 5 years with an 84.9% local control rate; 63.7% are alive and well, and 9.1% have died of intercurrent disease. An additional 22 patients have been treated with this regimen for recurrent rectal disease and 9.9% are alive and well at 5 years. Radiation therapy combined with 5-FU and Mitomycin-C for sensitization purposes appears to be effective in downstaging rectal carcinoma at surgery with a resultant survival rate superior to that following surgery alone.

The use of endocavitary irradiation for selected carcinomas of the rectum: ten years experience.

Since July, 1973, endocavitary irradiation has been used to treat 129 patients with rectal carcinoma. The lesion must be a modified Dukes' A, well-differentiated adenocarcinoma and no more than 5 cm in diameter and within 12 cm of the anal verge. Specialized diagnostic techniques assist with the clinical selection. Specially designed proctoscopes are used to visualize the carcinoma which is treated by a Philips RT-50 contact machine. 11000-12000 cGy are delivered in four treatments administered at 2-3 weekly intervals. No systemic side effects have been observed and local morbidity is minimal. This treatment preserves the anal sphincter, and sexual function in male patients. Hospitalization is not required and there is no risk of mortality. Recurrence has been observed in six of 129 patients within 18 months of treatment for known reasons. Two of these six patients have died from disease and a further 25 from other causes. The local control rate is 95.3%. This treatment modality has been offered also to 87 patients for palliation and this has been effectively obtained in 82.7%. This technique is an alternative to surgery in selected cases.

Preoperative radiation therapy with sensitizers in the management of carcinoma of the rectum.

There is enough evidence to show that adjuvant radiation therapy contributes to the management of patients with carcinoma of the rectum. In an effort to improve resectability and possibly survival rates, the use of chemosensitizers, combined with moderate doses of radiation used presurgically, was introduced for carcinomas larger than 5 cm in diameter requiring abdominoperineal resection. Based on our experience and that of others, it is believed that the method of administration of 5FU and mitomycin-C is an important factor in obtaining an increased therapeutic ratio. Because of the locoregional pattern of spread of rectal cancer, this adjuvant approach would appear suitable. A series of approximately 60 patients is discussed and the surgical findings and five-year survival is reported.