Sphincter preservation in rectal cancer. Preoperative radiation therapy followed by local excision.

Radiation therapy followed by local excision results in local control rates that appear comparable to those of local excision alone (in highly selected patients) or local excision followed by adjuvant radiation therapy. A significant drawback of this approach, however, is the potential loss of important histological information, such as risk of lymph node metastasis, depth of tumor penetration, and presence of lymphatic or vascular invasion. Radiation therapy followed by local excision may be an option for treatment of more advanced T3 rectal cancers in patients who either refuse radical surgery or are medically unfit. The available data in the literature do not support the routine use of local excision after radiation therapy in otherwise healthy patients with locally advanced rectal cancer.

Long-term results of preoperative radiation therapy alone for stage T3 and T4 rectal cancer.

BACKGROUND: There has been a resurgence of interest in the use of preoperative radiation therapy, with or without chemotherapy, for locally advanced rectal cancer. The purpose of this study was to analyse the time course and pattern of failure for 74 patients with clinical stage T3 or T4 (cT3-4) rectal cancer treated with preoperative radiation therapy for whom long-term follow-up was available. METHODS: Seventy-four patients with cT3-4 rectal cancer received a median of 45.0 Gy radiation alone followed by surgery 4-8 weeks later. Median follow-up was 90 months; two-thirds of patients were followed for at least 60 months. RESULTS: Following radiation therapy the pathological stage was 4 per cent pT0, 26 per cent pT1-2 and 70 per cent pT3-4. Thirty-two per cent had involved lymph nodes. The actuarial 5-year rates of local control, freedom from distant metastasis and disease-specific survival were 80, 64 and 73 per cent respectively. The corresponding 10-year rates were 73, 51 and 50 per cent. Median times to detection of local and distant recurrence were 34 and 24 months respectively. Eighty per cent of local recurrences were detected within 54 months; 80 per cent of distant recurrences were detected within 57 months. CONCLUSION: In this analysis, the time to detection of both local and distant recurrences following preoperative radiation therapy for advanced rectal cancer was surprisingly long. Almost 5 years (57 months) of follow-up were required to detect 80 per cent of all failures. The 5-year local control rate of 80 per cent compares favourably with that achieved by more aggressive chemoradiation regimens for fixed cancers; however, the high distant failure rate with radiation therapy alone suggests that adjuvant systemic therapy should be investigated.

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.

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.

Respiration-induced motion of the kidneys in whole abdominal radiotherapy: implications for treatment planning and late toxicity.

PURPOSE: Whole abdominal radiotherapy (WAR) has potential utility in the management of several malignancies. The limited radiation tolerance of the kidneys is an important consideration in the design of WAR fields. Although renal blocking is standard for WAR, few guidelines exist in the literature to factor respiration-induced kidney motion into the design of these blocks. METHODS: Radiographs were obtained to measure kidney excursion under forced respiratory conditions in eight patients (14 visualized kidneys). Intravenous contrast was administered and AP films were obtained at maximum inspiration and expiration. Renal excursion was measured relative to a horizontal reference line at the bottom of the L3 vertebral body. The kidney position on the actual treatment simulation film was also determined using this technique. Treatment isodose distributions through the kidneys were obtained for a sample patient using phantom measurements and two blocking schemes: AP/PA and PA only. These provided quantification of the actual dose received by the kidney in a typical WAR treatment. RESULTS: In the worst case scenario, the left kidney block required an additional 10 mm above and 15 mm below the renal silhouette on the simulation film in order to account for all phases of respiration. The corresponding values for the right kidney were 2 mm and 19 mm, respectively. The dose received by the kidney under the center of the block was 20% of prescribed using AP/PA blocks and 50% of prescribed using PA blocks only. However, portions of 'blocked' kidney received up to 90% of the prescribed dose with either technique. CONCLUSIONS: Although kidney motion under forced respiratory conditions is not representative of typical treatment conditions, the data highlight the possibility of renal movement during treatment. This is particularly important in light of the significant dose (20 to 50%) delivered to the kidney under the center of the kidney block of typical treatments. Given the potential for overdosage of this critical organ, careful prospective documentation of renal function is warranted in patients receiving WAR.

Endosonographic and color Doppler flow imaging alterations observed within irradiate rectal cancer.

PURPOSE: To correlate the endosonographic and color Doppler flow imaging alterations observed in irradiated rectal cancers with the pathologic features of radiation response, and to evaluate the potential impact of altered blood flow on the integrity of the surgical anastomosis. METHODS AND MATERIALS: Endosonography with color and pulsed wave Doppler was performed on 20 rectal cancer masses before and after high dose preoperative radiation (XRT). Pre- and post-XRT observations included comparing alterations in tumor size, sonographic echotexture, color Doppler flow, and pulsatility indices. Comparisons were made with pathologic findings in the irradiated specimens and with the incidence of anastomotic failure. RESULTS: Compared to pre-XRT observations, irradiated rectal cancers decreased in size and became either mixed in echogenicity with less apparent color Doppler flow (16 of 20) or unchanged in color Doppler flow and echotexture (4 of 20). Those with less flow (16 of 20) were imaged later (mean = 90.2 +/- 12.1 days) than those without change in color Doppler flow (mean = 21.7 +/- 2.7 days). Pathologically, the group of four without change in color Doppler signal had features of acute inflammation which were not observed in 16 of 20 imaged later. Based on pulsatility index measurements, both high and low resistance vessels were detected and confirmed by immunohistochemical staining, and features of postradiation obliterative vasculitis were observed. Only one primary anastomosis in 14 patients with decreased flow failed. CONCLUSIONS: The sonographic and color Doppler flow imaging alterations observed within irradiated rectal cancer correlated with changes of postradiation obliterative vasculitis. The apparent diminished local blood flow within high and low resistance vessels post-XRT did not result in an increased incidence of anastomotic failures.

Long-term follow-up of local excision and radiation therapy for invasive rectal cancer.

PURPOSE: Little is known regarding the long-term outcome of patients with rectal cancer treated by local excision and radiation therapy. We updated our institutional experience with this approach. METHODS: From January 1986 to December 1991, 23 patients (median age, 64 (range, 30-80) years) with mobile, moderately differentiated adenocarcinoma of the rectum were offered transanal excision. Two patients with large T3 tumors, who were judged intraoperatively to be unsuited for a local procedure, received radical resection and were excluded from analysis. Twenty-one patients underwent transanal excision en bloc (14) or piece-meal (7) through a resectoscope. Seven patients (74 percent) had either extensive medical problems or refused a colostomy. Patients received a median of 5,040 cGy postoperatively, and 15 also received 500 cGy preoperatively on protocol. Two patients received concomitant chemotherapy. Median follow-up is 56 months for all patients and 67 months for survivors (range, 27-92 months). RESULTS: There were 2 T1, 15 T2, and 4 T3 tumors. The distance from the anal verge was a median of 4 (range, 1-7) cm. The median tumor size was 3 (range, 2-7) cm. Sixteen patients had more than one-third of the wall involved. Four patients (19 percent) developed a local recurrence at 26, 30, 33, and 48 (median, 31.5) months. Three were salvaged (abdominoperineal resection = 2; low anterior resection = 1) and remain disease-free 18, 36, and 37 months postoperatively. Four patients (19 percent) developed metastases (lung = 3; liver = 1) at 3, 22, 25 and 44 months after initial treatment (median, 23.5 months). The actuarial five-year overall, disease-free and recurrence-free survival are 77, 75, and 58 percent, respectively. Twelve patients (57 percent) have no evidence of disease while retaining their rectum. There was one postoperative death. CONCLUSIONS: Long-term follow-up confirms that local excision and radiation therapy is of value in patients with mobile tumors of the rectum. It suggests that this treatment can be offered to those patients who refuse a colostomy or are medically compromised and may be an acceptable option for selected patients with T2 or T3, mobile adenocarcinomas of the rectum.

Postoperative radiation therapy for surgically staged endometrial cancer: impact of time factors (overall treatment time and surgery-to-radiation interval) on outcome.

PURPOSE: To evaluate the impact of prolonged overall radiation treatment (RT) time and surgery-to-radiation interval on local control (LC) and disease-specific survival (DSS) of surgically staged endometrial cancer patients in relation to known prognostic factors. METHODS AND MATERIALS: Between 1971 and 1993, 195 endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. All patients underwent total abdominal hysterectomy (TAH), with 38% also having lymph node sampling. All patients received whole pelvic external beam RT to a median dose of 45 Gy (range 40 to 60 Gy). Sixty-nine percent received a vaginal cuff boost with either low dose rate or high dose rate brachytherapy. Tumor and treatment factors were analyzed for impact on LC and DSS. Median follow-up was 47 months (range: 6 to 187 months). RESULTS: The overall actuarial 5-year LC rate was 85%. In multivariate analysis, tumor grade, pathologic stage, external radiation dose, and surgical lymph node evaluation were independent prognostic variables for improved LC. Surgery-to-radiation interval of greater than 6 weeks was a marginally significant factor for decreased LC (p = 0.06). Overall RT time and external beam treatment time did not appear to impact LC rates. The overall actuarial 5-year DSS rate was 86%. In multivariate analysis, depth of myometrial invasion, tumor grade, and pathologic stage were independent prognostic variables for DSS. In addition, a surgery-to-radiation interval of greater than 6 weeks was significantly associated with decreased DSS (p < 0.005). CONCLUSIONS: Surgery-to-radiation interval of greater than 6 weeks is a significant independent prognostic variable for decreased DSS and a marginally significant variable for decreased LC in patients irradiated postoperatively for endometrial cancer. Other time factors (overall RT time and external beam treatment time) did not appear to impact outcome. Based on this analysis, postoperative radiation therapy for endometrial cancer should be initiated within 6 weeks following surgery.

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.