High-dose Preoperative Radiation Research Articles

Radical and local excisional methods of sphincter-sparing surgery after high-dose radiation for cancer of the distal 3 cm of the rectum

Background: Despite conventional attitudes that interdict sphincter-preservation surgery (SPS) for cancers arising in the terminal 3 cm of rectum, we have selectively employed high-dose preoperative external radiation (HDPER) and either radical or local excisional SPS techniques for rectal cancer arising between the 0.5 and 3 cm levels above the anorectal ring. We have reported a preliminary experience with HDPER and full-thickness local excision (FTLE) and three different methods of radical SPS. We now describe our experience with a single method of radical excision, transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) and FTLE in conjunction with HDPER for cancers of the distal 3 cm of rectum based on specific guidelines.

Tumor proliferation in rectal cancer following preoperative irradiation.

This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer. One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf). Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome. There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies. Postirradiation tumor proliferative activity was associated with pathologic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4). Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. Patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. Moderate- to high-dose preoperative irradiation decreases both the tumor size and proliferative activity of rectal cancers. Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery.

Radical and local excisional methods of sphincter-sparing surgery after high-dose radiation for cancer of the distal 3 cm of the rectum

Despite conventional attitudes that interdict sphincter-preservation surgery (SPS) for cancers arising in the terminal 3 cm of rectum, we have selectively employed high-dose preoperative external radiation (HDPER) and either radical or local excisional SPS techniques for rectal cancer arising between the 0.5 and 3 cm levels above the anorectal ring. We have reported a preliminary experience with HDPER and full-thickness local excision (FTLE) and three different methods of radical SPS. We now describe our experience with a single method of radical excision, transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) and FTLE in conjunction with HDPER for cancers of the distal 3 cm of rectum based on specific guidelines. Since 1984, 109 patients with cancers at or below the 3 cm level have been treated with HDPER in doses of 4,500-7,000 cGy and a sphincter-preserving radical or local excision method in a prospective rectal cancer management program. Sixty-five patients (group A) underwent transanal abdominal transanal radical proctosigmoidectomy with colonal anastomosis (TATA) and 44 patients (group B) underwent FTLE. There was one death (1%). Mean follow-up was 40 months. Local recurrence rates for groups A and B were 9 and 14%, respectively. Kaplan-Meier 5-year actuarial survival was 85 and 90% for groups A and B, respectively, and 87% collectively. Experience with 109 patients with cancers of the distal 3 cm of rectum indicates that SPS can be accomplished by either radical or local excisional methods with acceptable local control and survival if HDPER and strict selection guidelines are employed.

Conservative surgery for low rectal carcinoma after high-dose radiation. Functional and oncologic results.

Using a prospective, nonrandomized study, the authors evaluated the morbidity and functional and oncologic results of conservative surgery for cancer of the lower third of the rectum after high-dose radiation. Colo-anal anastomosis has made sphincter conservation for low rectal carcinoma technically feasible. The limits to conservative surgery currently are oncologic rather than technical. Adjuvant radiotherapy has proven its benefit in terms of regional control, with a dose relationship. Since June 1990, 27 patients with distal rectal adenocarcinoma were treated by preoperative radiotherapy (40 + 20 Gy delivered with three fields) and curative surgery. The mean distance from the anal verge was 47 mm (27-57 mm), and none of the tumors were fixed (15 T2, 12 T3). Mortality and morbidity were not increased by high-dose preoperative radiation. Twenty-one patients underwent conservative surgery (78%-17 total proctectomies and colo-anal anastomoses, 4 trans-anal resections). After colo-anal anastomosis, all patients with colonic pouch had good results; two patients had moderate results and one patient had poor results after straight colo-anal anastomosis. With a mean follow-up of 24 months, the authors noted 1 postoperative death, 2 disease-linked deaths, 1 controlled regional recurrence, 2 evolutive patients with pulmonary metastases, and 21 disease-free patients. These first results confirm the possibility of conservative surgery for low rectal carcinoma after high-dose radiation. A prospective, randomized trial could be induced to determine the real role of the 20 Gy boost on the sphincter-saving decision.

35 High dose preoperative radiation and sphincter preservation surgery for cancer of the distal 2 cm of the rectum: The ultimate challenge

35 High dose preoperative radiation and sphincter preservation surgery for cancer of the distal 2 cm of the rectum: The ultimate challenge

High-dose preoperative radiation and full thickness local excision: A new option for selected T3 distal rectal cancers

Purpose: To assess the efficacy of high-dose preoperative radiation and full thickness local excision as an option for the management of selected distal rectal cancers. Methods and Materials: Forty-eight patients with invasive distal rectal cancer have been treated with high-dose preoperative radiation (45–55 GY at 180 cGy/fx) followed 6 to 8 weeks later by full thickness local excision. Three groups of patients are included in this study. Group 1 ( N = 15) Medically Compromised: patients with rectal cancers Stages T3 or > 3 cm in size and significant cardiorespiratory disease that precluded radical surgery. Group 2 ( N = 18) Elective: patients suitable for local treatment by standard criteria (Stages < T2 and < 3 cm in size), and group 3 ( N = 15) Staged: patients with Stages T3 or > 3 cm in size that postradiation were downstaged and met the criteria as in group 2. One patient in group 3 was found to be pathologically T3 following full thickness local excision and was converted to an abdominoperineal resection. Follow-up ranges from 6–96 months with a median of 40 months. Results: The overall 5-year actuarial survival for the whole group is 83.5% and local recurrence is 10%. The 5-year survival is 74%, 92%, and 88% for Groups 1, 2, and 3 and 90%, 89%, and 50% for postradiation pathologic stages TO/T1, T2. and T3, respectively. Local recurrence rate by treatment groups are 20%, 11%, and 0% for groups 1, 2, and 3 and 11%, 0%, and 67% for postradiation Stages TO/T1, T2, and T3, respectively. Surgical complications, primarily wound healing, were observed in five patients (10%). Four patients required a subsequent colostomy (three for recurrence and one for a rectovaginal fistula). Sphincter function as measured by Parks criteria was good/excellent in 88% of patients. Conclusion: High-dose preoperative radiation and full thickness local excision appear to be a promising new option for the management of selected patients with invasive distal rectal cancers. Selected patients with Stage T3 cancers that as a result of preoperative radiation are downstaged and met the criteria for primary local therapy (T2 or less) appear to have an excellent survival with retained normal sphincter function following full thickness local excision.

Superior sulcus tumors: Combined modality

Twenty-four patients with superior sulcus tumors were seen between 1955 and 1989. Fifteen of these patients received combined-modality therapy. In 2 patients, this consisted of primary operation followed by postoperative radiotherapy, and, in 13, high-dose conventionally fractionated preoperative radiotherapy (5,500 to 6,475 cGy) followed by en bloc resection. Of the 13 patients who received radiotherapy preopeiatively, 7 survived free of disease beyond 5 years and 2 others remained without evidence of disease after a shorter follow-up (greater than 2 years). The long-term survival in the combined-modality patients in this small series is superior to that reported for other patients receiving combined-modality therapy, and the morbidity appears to be within accepted limits despite the aggressive preoperative radiotherapy program. One postoperative death occurred in our only octogenarian, but there wen no other acute complications. High-dose preoperative radiotherapy using current techniques and fractionation appears to be feasible in conjunction with contemporary surgical techniques. We believe this type of preoperative radiotherapy contributed to the apparent superior survival rate in this series and may also be applicable in the setting of other locally advanced (stage III) bronchogenic carcinomas.

The clinical staging of rectal cancer in patients treated by preoperative radiotherapy

We describe the results of clinical and (or) surgical staging used by the same surgeon to select a group of 41 patients with advanced rectal cancer for preoperative radiotherapy. Fifteen patients with resectable but advanced rectal cancer were subjected to a short course of radiotherapy (30 Gy in 10 days), immediately followed by resection. High dose preoperative radiotherapy (50–56 Gy in 5 weeks) was administered to 26 patients with borderline resectable or fixed cancer. Adequate resection of the tumour was possible in 21 of these 26 patients 4 weeks after the end of the radiotherapy. A total of 36 patients thus underwent resection after preoperative radiotherapy. No radiotherapy related acute or late morbidity was seen. On 31 December 1992 the results were investigated retrospectively. The median time since entering into the study was 87 months (range 27–141). During the follow-up, pelvic recurrence was detected in six patients; one patient had concomitant distant metastases. The local recurrence free survival at 5 years calculated by the Kaplan-Meier method was 72% (95% CI 58–85). Distant metastases without local recurrence developed in 11 patients. The calculated survival at 5 years was 45% (95% CI 30.5–59).

The reality of radical sphincter preservation surgery for cancer of the distal 3 cm of rectum following high-dose radiation

Purpose : The inordinately high rate of locoregional recurrence following sphincter-preserving surgery for cancer of the distal rectum led to the conviction that restorative surgery was inappropriate for the low level cancer. A rectal cancer management program initiated in 1976 that selectively uses high-dose preoperative radiation and sphincter-preserving surgery produced lower than expected local recurrence rates. Exploring the safety of extending the indication for sphincter-sparing surgery to include post-radiation mobile cancers as low as the 0.5 cm level is the purpose of this report. Methods and Materials : Of 218 rectal cancer patients treated with high-dose preoperative radiation and sphincter-preserving procedures, 69 had radical curative surgery for cancers at or below the 3 cm level. Data regarding the first 52 patients whose ages ranged from 39 to 77 years form the basis of this report. Fifty-seven percent were men. Twenty-five (48%) patients had post-radiation unfavorable cancers (B2, Cl, C2). Forty-five to sixty Gy high energy photon radiation was administered over 4 1 2 to 6 weeks followed by a similar interval prior to radical proctosigmoidectomy with anastomosis in the distal 1 cm of rectum. Temporary fecal diversion was performed in all patients; colostomies were closed after 8 weeks. Results : There was zero mortality and two self-limiting anastomotic leaks. Local recurrence developed in 6 43 (14%) patients followed for 24 months or longer. By stage, there were 0 21 (0%) recurrences among O, A, B1 tumors; 6 22 (27%) among unfavorable tumors. By distal margins, 1 9 (11%) occurred in .3 – 1 cm; 4/13 (31%) 1.1–2 cm; 1 18 (5%) 2.1–3 cm. Five-year Kaplan Meier actuarial survival for the 52 patients was 85%. Conclusion : Our data indicates that sphincter preservation can be accomplished in cancers of the distal 3 cm of rectum if high-dose preoperative radiation is administered and fixed cancers are excluded. This is the first reported study of sphincter-preserving surgery for the distal rectal cancer after high-dose radiation. The data are important to the design of new treatment options.

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.

Patterns of recurrence following high-dose preoperative radiation and sphincter-preserving surgery for cancer of the rectum

High-dose preoperative radiation with new sphincter-preserving surgical options for the management of distal and unfavorable cancers of the rectum is gaining recognition as an alternative to abdominoperineal resection and permanent colostomy. From 1976 to 1989, 161 patients with cancer of the rectum were entered into a program of high-dose preoperative radiation and radical sphincter-preserving surgery. Selection was based on prospective clinical staging of unfavorability or tumor location at a low level in the rectum. All patients received a minimum dose of 4,000 to 4,500 cGy over 4 1/2 weeks in fractional doses of 180 to 250 cGy. Patients with tumor fixation were given an additional boost of 1,000 to 1,500 cGy for a total of 5,500 to 6,000 cGy using a coned-down field. Surgery was carried out four to eight weeks following completion of radiation. Fourteen patients, found at surgery to have liver metastasis, were treated by palliative resection. One hundred forty-seven patients underwent radical curative surgery with sphincter preservation. The surgical procedures performed were combined abdominotranssacral resection (63), transanal-abdominal-transanal resection (53), and anterior resection (31). Follow-up ranged from a minimum of two years to 15 years, with a median of five years. There was no perioperative mortality. Anastomotic failure occurred in three patients, two of whom were reconstituted. Late diversion was required in 10 other patients, primarily for recurrent disease. One hundred thirty-four of the 147 patients (91 percent) maintained long-term normal sphincter function. Pelvic-perineal recurrence was observed in 18 patients (12.4 percent), 12 of whom had fixed tumors located below the 6-cm level of the distal rectum. Median time to local recurrence was 24 months. Distant metastasis with or without local recurrence occurred in 35 patients, 22 of whom had fixed tumors below the 6-cm level of the rectum. Median time to distant metastasis was 17 months. Forty-three patients have died, 32 of disease. The overall five-year Kaplan-Meier actuarial survival for the total group of patients is 79 percent, with a disease-free survival of 73 percent. The findings of this study indicate that high-dose preoperative radiation used in combination with radical sphincter-preserving surgical techniques results in excellent local control of disease, improved survival, and enhanced quality of life with retention of normal anal sphincter function.

High dose preoperative radiation and full thickness local excision: A new option for selected T3 distal rectal cancers

High dose preoperative radiation and full thickness local excision: A new option for selected T3 distal rectal cancers

Few surgical complications after 5,000 to 6,500 cGy pre-operative irradiation for carcinoma of the tongue.

Twenty-four patients with squamous cell carcinoma of the tongue were treated with 5,000 cGy to 6,500 cGy pre-operative irradiation. Surgery usually consisted of resection of the tongue, possibly the floor of mouth, and modified or radical neck dissection. Musculocutaneous flaps for reconstruction were used in three cases and a forearm flap in one case. Despite the high radiation dose, no major difficulties were encountered at surgery or during the convalescence period, except for one osteoradionecrosis of the mandible, which was successfully treated by microvascular osteomyocutaneous grafting. Residual carcinoma was seen on histological examination of the excised tissue in 9 out of 18 (50 per cent) patients who received > or = 6,000 cGy, and in 4 out of 6 (67 per cent) patients who received about 5,000 cGy tumour dose. The 2-year crude survival rate was 65 per cent. The data suggest that high dose pre-operative irradiation is feasible and does not compromise surgical treatment.

High-Dose Preoperative Radiation Therapy as the Key to Extending Sphincter-Preservation Surgery for Cancer of the Distal Rectum

Cancers (N = 105) of the distal rectum (between the 0.5-cm and 6-cm level) were treated with high-dose preoperative radiation ( ^4500 cGy) and radical proctosigmoidectomy with sphincter preservation by three surgical techniques. There was no mortality and no perioperative radiation-related morbidity. Five-year Kaplan-Meier actuarial survival was 79%; postradiated favorable stages (O, Al, Bl) = 100%; and unfavorable stages (B2, Cl, C2) = 69%. Local recurrence followed 24 months or longer was 14 of 86 (16%), with zero recurrence in the postradiated favorable stages. The preoperative mode of high-dose radiation may be the key to sphincter-preservation surgery for cancer of the distal rectum.

Rectal carcinoma. Long-term experience with moderately high-dose preoperative radiation and low anterior resection.

This report updated an analysis of a 14-year experience of moderately high-dose (4500 to 5000 cGy) preoperative radiation as an adjuvant to low anterior resection of 95 cases of adenocarcinoma of the rectum. The treatment was well tolerated without treatment-related mortality and with a low incidence (5.2%) of severe complications. The local recurrence rate was 4.2%, and distant failure rate was 10.5%. At 5 years, the actuarial survival rate was 66% and the disease-free survival rate was 64%. At 10 years, the actuarial survival rate and disease-free survival rate were 52%. The authors concluded that moderately high-dose (4500 to 5000 cGy) neoadjuvant radiation in clinically resectable adenocarcinoma of the rectum in which one segment of the anastomosis was in the preoperative radiation field is a safe, effective adjuvant to low anterior resection and that it offered patients excellent local control, long-term survival, and sphincter preservation. Results could be enhanced by chemotherapy, and the authors urged well-designed prospective randomized multicenter trials to determine the most appropriate drugs, dosage, and sequencing of co-adjuvant preoperative radiation therapy and chemotherapy with surgery.

Preoperative radiation therapy for locally advanced carcinoma of the rectum

During a three-year period, 27 patients with the diagnosis of adenocarcinoma of the rectum were referred to the Department of Radiation Oncology and accepted for preoperative radiation therapy. The referral was based solely on endoluminal ultrasound staging (ELUS) of an unfavorable lesion (n = 12) or ultrasound staging with the clinical impression of a fixed (n = 9) or tethered (n = 6) lesion. High-dose (4,500-5,600 cGy) preoperative radiation was followed by definitive surgery in four to seven weeks. The gross and microscopic pathology observed in 23 specimens of this group of patients formed the basis of this report. The microscopic findings that persist after radiation allow an accurate determination of the tumor stage existing prior to radiation. Correlations are made between the original evaluation of the tumor, including ELUS, and the microscopic findings. ELUS accurately predicted the depth of tumor penetration in 20 to 23 of 23 specimens and the lymph node status in 16 of 23 specimens. In the context of the pathologic findings as described, downstaging was not demonstrated. Following this radiation protocol, a marked reduction in tumor mass was demonstrated, as well as evidence of tumor destruction in the remaining mass, varying from minimal to total elimination of viable tumor. The concept that radiation fibrosis exists only as it approximates or replaces neoplasm is offered. In the context of this pathologic finding, improved resectability occurred for certain tumors. It is recommended that ELUS be added to the clinical evaluation of rectal adenocarcinoma. It is also recommended that the pathologic findings described be used when reporting the stage of rectal tumors that have received high-dose preoperative radiation therapy.

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

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

The reality of radical sphincter preservation surgery for cancer of the distal 3 CMS of rectum utilizing high dose preoperative radiation

The reality of radical sphincter preservation surgery for cancer of the distal 3 CMS of rectum utilizing high dose preoperative radiation

直腸癌に対する手術前大量放射線照射後の組織学的変化および局所再発防止に対する効果

直腸癌に対する手術前大量放射線照射後の組織学的変化および局所再発防止に対する効果

High-Dose Preoperative Radiation and Radical Sphincter-Preserving Surgery for Rectal Cancer

To reduce local recurrence associated with rectal cancer and to extend the scope of anal sphincter preservation, a selective program of high-dose preoperative radiation therapy and sphincter-preserving surgery was initiated in 1976. High-energy photon therapy (40 to 60 Gy) was administered in doses of 1.8 to 2.5 Gy during a period of 4 1/2 to 6 weeks and followed in 4 to 6 weeks with curative sphincter-preserving surgery for clinicopathologically unfavorable and low rectal cancers. None of the 143 patients in the study died during the postoperative period. Fifteen (13%) of 117 patients followed up for at least 24 months experienced local recurrence. Acceptable sphincter function was retained in 130 patients (91%). Our program of high-dose preoperative radiation therapy and sphincter-preserving surgery for the treatment of high-risk cancers, including those in the distal third of the rectum, resulted in better-than-expected survival and control of local recurrence with acceptable morbidity and no mortality.