High dose preoperative radiation and sphincter preservation in the treatment of rectal cancer

Abdominoperineal resection and permanent colostomy have been the mainstay of treatment for rectal cancer. Automatic stapling devices have widened the scope of low anterior resection, permitting sphincter preservation for tumors originating in the upper and middle thirds of the rectum. Attempts at sphincter preservation in low rectal cancer has resulted in higher recurrence in the pelvic/perineal tissues (41%, MSKCC). In 1976, we undertook a study to expand the scope of sphincter preservation in patients with rectal cancer. Patients were selected because of the presence of unfavorable tumors or low level of rectal area (3 and 6 cm from the dentate line). Forty-three patients were treated in this program. Follow-up ranges from 24 to 96 months, with a median follow-up of 36 months. Fifteen patients were selected for unfavorable tumor types and 28 patients were selected for low level of tumor, between 3 and 6 cm. Twenty of the 28 patients with low level tumors also had unfavorable tumors. All patients received the full course of preoperative radiation (4000 to 4500 cGy in 5 weeks). Surgery was carried out 4 to 6 weeks following radiation and consisted of a sphincter saving procedure, usually by combined abdominotranssacral resection. There was no perioperative mortality. A single anastomotic breakdown required reconstruction. Thirteen patients in this group have died, 9 of these with disease and 3 without evidence of tumor. There were 6 (14%) local recurrences in the pelvic/perineal area. Survival of all patients at 4 years is 66%. This early experience indicates that the high dose preoperative radiation can minimize local recurrence in unfavorable cancers and allows sphincter saving surgery to be performed with small, safe margins in the lower rectal cancers.     

Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up

Background: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer.Methods: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T_2; 31,T₃) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5–7 cm] and the median distance from the anal verge was 4 cm [range: 3–7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4–121 months].Results: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0–8).Conclusions: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T₃ disease.     

High dose preoperative irradiation for cancer of the rectum, 1976-1988

Two hundred twenty patients with adenocarcinoma of the rectum have been treated in a program using high dose (greater than 4000 cGy) preoperative irradiation followed by radical surgical resection. The patients were staged on the basis of pretreatment clinical mobility of the cancers. Seventy-four patients had mobile cancers, 49 had partial fixation (tethered), 85 patients had total tumor fixation, and 12 patients had a frozen pelvis (unresectable). Patients were treated with high energy photons using a four field box technique with total doses ranging from 4000 to 6000 cGy. The overall incidence of local recurrence was 15% (32/220). Patients with fixed and unresectable tumors had a higher incidence of local recurrence, 20% (21/97) as compared with patients with mobile and partially fixed tumors, 10% (13/123). Local recurrence by pathological stage of disease was 6% for patients with Stages O, A, B1 versus 20% for patients with Stages B2 and C cancer. Overall 5-year survival of the total group was 67%. The 5-year survival by clinical stages of disease was 87% for mobile tumors, 74% for partially fixed tumors, 70% for fixed tumors, and 22% for the unresectable group. The 5-year survival by pathological stages of disease was 90% for those with Stage O, A, B1 and 71, 75, and 47%, respectively, for Stages B2, C1, and C2 disease.     

Sphincter preservation in rectal cancer

Opinion statement Distal rectal cancer poses two challenges to the oncologist: local tumor control and sphincter preservation. The abdominoperineal resection (APR), long considered the standard treatment of tumors with a distal edge located up to 6 cm from the anal verge, provides local control in many patients but results in sphincter loss with a permanent colostomy. This is a critical limitation. Consequently, there has been significant interest in sphincter-conserving approaches, frequently combining chemoradiation with surgery. These approaches have evolved along two fronts. For patients with small rectal cancers confined to the rectal wall, local excision techniques with and without chemoradiation may offer comparable local control and survival rates as an APR and preserve sphincter function. For patients with larger and more invasive tumors of the distal rectum where local excision is inappropriate, preoperative chemoradiation promotes tumor regression and may facilitate a resection sparing the sphincter with a coloanal anastomosis. Preliminary results from single institution studies appear promising. In both these settings (favorable and more invasive rectal cancer), chemoradiation is employed to compensate for the limitations of the sphincter-preserving surgical technique. In local excision procedures, the excision margins are invariably small, and the mesorectum (lymphatics, soft tissue) surrounding the tumor is not excised. For patients undergoing resection with coloanal anastomosis, there are narrow radial and distal surgical margins. With these approaches of chemoradiation and sphinctersparing surgery, satisfactory local control and survival with avoidance of colostomy are possible for many patients with distal rectal cancer.     

Sphincter preservation in rectal cancer

Sphincter preservation is a major goal in the treatment of rectal cancer. For selected patients with T1–2 disease, local excision followed by postoperative combined modality therapy is a reasonable alternative to an abdominoperineal resection. However, for patients with T3 disease, the local recurrence with this approach is approximately 25% and they are treated more effectively with preoperative combined modality therapy. In patients who undergo a prospective clinical assessment and are declared to require an abdominoperineal resection, preoperative radiation therapy, either alone or when combined with chemotherapy, allows approximately 80% to undergo a low anterior resection/coloanal anastomosis. The majority have good-to-excellent sphincter function. These conservative approaches may be an alternative to an abdominoperineal resection in selected patients. Received: August 7, 1998     

Sphincter and rectal preservation approaches for early stage distal rectal cancers

In rectal cancer, the problem of sphincter preservation is of increasing interest. This paper is a review of recent data regarding sphincter preservation. Randomized trials give the best evidence of any improvement in sphincter preservation. Such trials have been performed for T3 and T2 rectal cancers. For T2-3 rectal tumors immediate surgery after preoperative radiotherapy or the addition of chemotherapy to radiotherapy did not improve the chance of sphincter preservation. Only dose escalation with endocavitary contact x-ray and delayed surgery was able to achieve a 30% increase in sphincter preservation. Ongoing clinical research is exploring the role of preoperative chemoradiotherapy in early T2 (T3) rectal cancers combined with local excision. This approach is of special interest in elderly patients. Sphincter preservation is a very complex issue in rectal cancer requiring great clinical experience to select properly the patients to perform the optimal treatment.     

Role of preoperative radiotherapy in preservation of the anal sphincter in cancer of the lower rectum

Short term preoperative irradiation of rectal cancer (30 Gy in 12 days) followed by a two-month rest before surgery has proven to be more efficient than most usual protocols of radiotherapy. In a series of 136 tumors T2, T3 or T4, tumor-free specimens and Duke'A lesions were found at surgery in 17% and 36% respectively. Surgeons took advantage of the tumor regression and performed sphincter-saving surgery in 41 patients with T2, T3 or T4 tumors of the lower third of the rectum. Of 30 patients followed from 2 to 6 years, the disease-free survival rate is 86%. Only one local failure was observed and subsequently controlled by abdomino-perineal resection.     

Survival following moderate-dose preoperative radiation therapy for carcinoma of the rectum

We performed a retrospective study of patients with carcinoma of the rectum or rectosigmoid undergoing surgical resection. Forty-two patients received adjuvant preoperative radiation therapy (4000-4500 rad). One hundred twenty patients underwent surgical resection alone. Survival of radiation patients was significantly improved over that of Surgery Only patients, even after adjusting for nontreatment factors using Cox regression. Crude 5-year survival was 63% for radiation patients (74% adjusted) compared to 46% for surgery-only patients (48% adjusted) (P less than 0.025). Radiation patients also had longer disease-free survival than surgery-only patients (P less than 0.05) and fewer recurrences (14% versus 37%; P less than 0.025). Fewer radiation patients had lymph nodes involved with tumor than surgery-only patients (20% versus 35%; P = 0.07). Although 71% of radiation patients experienced radiation reactions, these were primarily mild and transitory. We believe that preoperative radiation is an effective and safe adjunct to surgery in the treatment of rectal cancer and that its use can lead to improved survival rates.     

Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy.

BACKGROUND AND PURPOSE: The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Preliminary results of preoperative regional chemotherapy of cancer of the rectum

The results of combined treatment for rectal cancer including preoperative intraarterial chemotherapy are discussed. The study group showed a significant decrease in the frequency of local recurrence development, justifying the use of the said combination for treatment of locally-advanced rectal cancer.     

Strategy for dose escalation using 3-dimensional conformal radiation therapy for lung cancer

PURPOSE: Local failure is a major obstacle to the cure of locally advancednon-small-cell lung cancer. 3-Dimensional conformal radiationtherapy (3-DCRT) selects optimal treatment parameters to increasedose to tumor and reduce normal tissue dose, potentially permittingdose escalation. There are several ongoing trials of dose escalationusing 3-dimensional conformal radiation therapy for non-small-celllung cancer. We performed this analysis to determine if dataderived from dose volume histograms could be used as the basisfor designing the method of dose escalation in these trials. METHODS AND MATERIALS: Between 1990 and 1993, 31 patients were treated with 3-DCRTand had complete normal tissue dose volume histograms createdas part of the planning process. The stage distribution wasstage I/TI 13%, stage IHa in 45%, and stage Illb in 42%. Themedian radiation dose to gross disease was 70.2 Gy (52.2–;72Gy). Elective mediastinal irradiation (50.4 Gy) was administeredto 52% (16/31) of patients. RESULTS: Thr toxicity encountered in this experience was pulmonary. Dose-volume-histogramdata were used to analyze the predictors of toxicity and showeda correlation between risk of pulmonary toxicity and indicesof dose to lung parenchyma. Grade 3 or higher pulmonary toxicityoccurredin 38% (3/8) of pts with > 30% of lung volume receiving >25 Gy, versus 4% (1/23) of pts. with < 30% lung receiving> 25 Gy (p =0.04). Grade 3 or higher pulmonary toxicity occurredin 29% (4/14) of patients with a predicted pulmonary normaltissue complication probability of 12% or higher versus 0% (0/17)in patients with a predicted probability of less than 12% (p=0.03).The single fatality occurred in a patient with a calculatedpneumonitis probability of 85% and a high percent (49%) lungvolume receiving > = 25 Gy. CONCLUSION: This preliminary experience demonstrates a correlation betweenlung dose-volume-histogram data and the risk of severe pulmonarytoxicity. This provides an opportunity to modify the methodof radiation dose escalan. Dose-volume-histogram data can allowescalation according to the risk to the lung parenchyma (whichis the major organ of concern) rather than escalation accordingto tumor dose levels. Because of the major inter-patient variabilityof intrathoracic tumor bulk and anatomic distribution, thisstrategy is intuitively appropriate. This approach may facilitatecompletion of dose escalation studies and identification ofmaximum tolerable pulmonary dose levels. lung cancer, radiation, 3-dimensional treatment planning     

Prostate displacement kit: reducing the radiation dose to the rectum.

During high dose-rate brachytherapy boost in 20 patients the use of a prostate-water-rectal-displacement-kit contributed to an increase in the distance between the prostate and the rectum, however, the prostate was not totally immobilized by the needles, implying the necessity for an very careful on-line dose-planning dosimetry.     

早期乳腺癌保留乳房术后外照射加组织间插植放疗

12例早期乳腺癌患者行乳房肿瘤扩大切除术后,配合外照射加组织间插植高剂量率近距离放疗,患侧胸壁 外照射剂量40～57Gy,局部组织间插植近距离放疗剂量6～22Gy/1～4F。8例随访满5年,5年生存率8/8,局部控 制率91.7%(11/12),1例出现照射野内一处肋骨骨折,1例乳房胸壁纤维化,美容效果满意率91.7%(11/12)。初步 研究结果提示,早期乳腺癌保守手术后外照射加组织间插植近距离放疗生存率与根治术相同,而且美容效果好。     

宫颈癌3DBT直肠实测剂量与参考剂量相关性研究

目的 探讨宫颈癌3DBT中直肠实测剂量与参考剂量的相关性, 评估直肠实测剂量的意义。方法 选取50例行宫颈癌根治性放疗患者, 在完成全盆腔外照射后行三维近距离治疗(3DBT)。依据ICRU38号报告推荐的直肠监测方法, 通过在体监测得到直肠实测剂量、参考点剂量(D_ICRU)及D_{2.0 cm³}, 在计划系统中得到计划剂量。应用配对t检验比较它们的差异, 采用Pearson法进行相关分析。结果 直肠实测剂量大于计划剂量(3.48∶3.25, P=0.000)、小于D_ICRU (3.48∶3.71, P=0.000)和D_{2.0 cm³}(3.48∶3.87, P=0.002)。直肠实测剂量与计划剂量存在线性关系, 二者偏差百分数为－20%~40%, 偏差平均数为8.16%, 其中63%宫颈癌患者偏差<±10%, 最大偏差达60%。实测剂量与D_ICRU相关性强(r=0.722)、与D_{2.0 cm³}相关性弱(r=0.284)。结论 宫颈癌3DBT中直肠实测剂量存在一定偏差, 但与计划剂量呈线性相关。实测剂量及计划剂量均会低估直肠剂量参考点剂量。直肠在体监测方法可作为有效的质量控制手段。