Clinical predictors of upgrading to Gleason grade 4 or 5 disease at radical prostatectomy: potential implications for patient selection for radiation and androgen suppression therapy

BACKGROUND: To determine the local control, survival, and functional outcome of local excision plus postoperative therapy for patients with rectal cancer. METHODS: A total of 39 patients underwent a local excision (2 with snare excision of a T1 polyp and 37 with full-thickness local excision) followed by postoperative radiation therapy +/- 5-FU-based chemotherapy. The median follow-up was 41 months, and 11 patients had positive margins. RESULTS: The 5-year actuarial colostomy-free survival was 87% and overall survival was 70%. Crude local failure increased with T stage: 0% T1, 24% T2, and 25% T3. Of the 8 patients (21%) who developed local failure, 5 underwent salvage APR and were locally controlled. Actuarial local failure at 5 years was 31% for T2 disease and 27% for the total patient group. In the 32 patients with an intact sphincter, 94% had good to excellent sphincter function. CONCLUSION: Although local failure in patients with T2 tumors has increased since our prior report, the survival, sphincter function, and local salvage rates are acceptable. Local excision and postoperative therapy remains a reasonable alternative to APR in selected patients.     

T2期低位直肠癌术前伊立替康化疗联合短程放疗后局部切除的可行性研究

目的 探讨术前伊立替康化疗联合短程放疗后局部切除术治疗T₂期低位直肠癌的可行性。方法 收集山西省肿瘤医院2002年1月至2008年8月间行术前伊立替康化疗联合短程放疗后行经肛门局部切除术（TAE）的37例低位直肠癌患者的临床资料,分析治疗疗效、不良反应及随访情况。结果 37例患者经术前治疗后4例（10.8％）获完全缓解,27例（73.0％）部分缓解,6例（16.2％）病情稳定,有效率为83.8％,疾病控制率为100.0％。37例患者术后出现肛门狭窄2例（5.4％）,出血和直肠阴道瘘各1例（2.7％）。至随访截止时间,共6例（16.2％）术后出现复发转移,其中3例为局部复发,2例为肝转移,1例局部复发伴肝转移;37例患者术后的3年、5年复发率分别为11.7％、14.1％;全组患者术后生存时间为26～118个月,3例患者因转移复发死亡,术后3年、5年生存率分别为94.6％、91.4％。结论对于符合条件的T₂期低位直肠癌患者,术前伊立替康化疗联合短程放疗后局部切除治疗可以作为临床选择方案之一。     

Local excision and postoperative radiotherapy for distal rectal cancer

To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma.

Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and “elective” where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1–8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38–60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3–5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10–165 months).

Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery).

The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.     

Sphincter preservation for cancer of the distal rectum using high dose preoperative radiation

Sphincter preservation surgery for cancer of the distal rectum is recognized as being associated with a high incidence of local recurrence. High dose preoperative radiation with new surgical techniques is described as an attempt to widen the scope of sphincter preservation in patients who by conventional management would have an abdomino-perineal resection and permanent colostomy and to reduce the incidence of local recurrence. Since 1976, 121 patients with cancers of the rectum have selectively been treated with high dose preoperative radiation (4000 cGy to 6000 cGy) followed by combined abdominotranssacral resection (56); transanal abdominotransanal resection (28); anterior resection (21), or a full thickness wide local excision (16). This report details the results of 43 patients observed for a minimum of 2 years whose tumors were located from 0-6 cm of the dentate line. All patients received the full course of preoperative radiation, a minimum dose of 4000-4500 cGy in approximately 4 1/2 weeks that was delivered using 180-250 cGy per fraction. Patients with tumor fixation were given an additional boost of 1000-1500 cGy preoperatively. Surgery was carried out 4-6 weeks following the completion of radiation. There was no perioperative mortality. Anastomotic failure occurred in 3 patients and was reconstituted in two. Sphincter function was maintained in all but 6 patients (86%), 2 of these had a subsequent abdominoperineal resection, and 3 a diverting colostomy. Seven of 43 (16%) patients with tumors below 6 cm developed a local recurrence, and 6 of the 7 recurrences occurred in patients with fixed tumors, especially those located from 0-3 cm from the dentate line. Eleven patients are dead of disease. The 5-year actuarial survival rate for this group is 72%. Results indicate that high dose preoperative radiation can significantly extend the scope of sphincter preservation to selected cancers of the disal rectum with excellent survival without increasing the risk of pelvic perineal recurrence.     

Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.     

Oncological outcomes of transanal local excision for high risk T(1) rectal cancers

AIM:To evaluate the oncological outcomes of transanal local excision and the need for immediate conventional reoperation in the treatment of patients with high risk T1 rectal cancers.METHODS:Twenty five high risk T1 rectal cancers treated by transanal local excision at the Guangdong General Hospital were analyzed retrospectively.Twelve patients received transanal local excision and 13 patients underwent subsequent immediate surgical rescue after transanal local excision within 4 wk.Differences in the local recurrence rates and 5-year overall survival rates between the two groups were analyzed.The prognostic value of immediate conventional reoperation for high risk T1 rectal cancers was also evaluated.RESULTS:The median follow-up period was 62 mo.The local recurrence rates after transanal local excisionfor high risk T1 rectal cancer were 50%.By immediate conventional reoperation,the local recurrence rates were significantly reduced to 7.7%.The difference between these two groups was statistically significant(P = 0.030).Kaplan-Meier survival analysis showed a trend for decreased 5-year overall survival rates for patients treated by transanal local excision compared with immediate conventional reoperation(63%vs 89%).CONCLUSION:Transanal local excision cannot be considered sufficient treatment for patients with high risk T1 rectal cancers.Immediate conventional reoperation should be performed if the pathology of the local excision is high risk.     

腔镜直线切割吻合器用于T1期中低位直肠癌经肛门局部切除术的疗效及安全性

目的:探讨应用腔镜直线切割吻合器（endoscopic linear cutters,ENDOPATH）行经肛门局部切除术治疗T1期中低位直肠癌的疗效和安全性。方法:回顾性分析2011年01月至2017年12月我院收治的92例T1期中低位直肠癌患者的临床资料。根据手术方式分为经肛门局部切除术组（TAE组）与直肠癌传统根治术组（根治术组）。TAE组使用腔镜直线切割吻合器行经肛门全层局部切除术,共39例;根治术组按全直肠系膜切除原则行传统根治术,共53例(包括16例Miles手术和37例Dixon手术)。对两组患者的一般资料、术中及术后相关指标及预后情况进行比较。结果:TAE组和根治术组患者在性别、年龄、肿瘤病理分型、肿瘤大小、距肛缘距离方面对比分析,无显著性差异（P＞0.05）,两组资料有可比性。两组患者在手术时间［（TAE组:(37.74±10.66)min,根治术组:(117.66±41.78)min］、术后住院时间［TAE组:(6.85±1.06)天,根治术组:(10.70±1.72)天］、术中出血量［TAE组:(30.21±2.97)mL,根治术组:(78.96±12.65)mL］、术后并发症发生率（TAE组:2.56%,根治术组:43.39%）方面差异均有统计学意义（P＜0.01)。两组患者的3年无病生存率均为100.00%,两组患者3年内均无复发,相比较无统计学差异（P＞0.05）。两组患者的生存质量评分［TAE组:(90.31±3.82)分,根治术组:（71.59±6.33）分］差异有统计学意义（P＜0.01)。结论:与传统根治术相比,应用腔镜直线切割吻合器对T1期中低位直肠癌行经肛门局部切除术同样安全有效。应用腔镜直线切割吻合器行经肛门局部切除术创伤小、并发症少、恢复快,患者术后生活质量等方面明显优于根治术。应用腔镜直线切割吻合器行经肛门局部切除术可作为早期无淋巴转移的中低位直肠癌患者优先选择的一种术式。     

影响低位直肠癌局部切除选择的因素分析

目的探讨低位直肠癌局部切除选择的影响因素。方法回顾性分析101例局部切除治疗低位直肠癌患者的临床资料。Kaplan-Meier法计算生存率,并对预后进行单因素及多因素分析。结果经肛门切除91例,经骶骨切除9例,经阴道切除1例,并发症发生率为5.9%,全组无手术死亡病例。术前放疗5例,术后放疗34例。5年生存率为91.0%,Tis、T1、T2及T3或T4病变的5年生存率分别为100%、92.6%、77.1%和83.3%;局部复发率为15.8%。单因素分析显示,肿瘤的侵袭深度、直径>3 cm、有脉管瘤栓、溃疡型癌、放射治疗和局部复发与预后有关(P<0.05)。多因素分析显示,肿瘤直径>3 cm、局部复发是影响预后最重要的因素(P<0.05)。结论低位直肠癌病理为高中分化、直径≤3 cm、无脉管瘤栓的T1病变及原位癌,是局部切除术的合理适应证。     

直肠类癌手术方式的探讨

目的探讨直肠类癌手术方式的合理选择。方法对我院1982年4月-2008年12月间手术治疗的51例直肠类癌病例进行回顾性研究及随访。结肠镜下肿瘤电切术3例,经肛门局部切除术13例,经肛门括约肌的直肠外科手术（Mason术）7例,经肛门内镜微创手术（TEM）18例,直肠前切除术（Dixon术）2例,经腹直肠切除经肛门结肠肛管吻合术（Parks术）2例,腹会阴联合直肠肿瘤切除术（Miles术）4例,其他手术2例。结果术后病理确诊直肠类癌残灶显慢性炎11例,直肠类癌局限于粘膜下层以内者（pT0或pT1期）28例,直肠恶性类癌（神经内分泌癌）12例（23．5％）。全组51例患者手术并发症的发生率为3．9％。12例直肠恶性类癌中1例Miles术后发生肝转移,2例经肛门切除术后复发。本组中7例Mason术和18例TEM术后均未发生并发症或肿瘤局部复发。结论选择直肠类癌的手术方式应综合考虑类癌的具体部位、大小以及术前活检的病理结果,对于疑诊恶性的病例还应考虑肿瘤浸润肠壁的深度。Mason术和TEM为适合局部切除的直肠类癌患者提供了理想的术式选择。     

Local excision of rectal carcinoma: a safe alternative for more advanced tumors?

BACKGROUND AND OBJECTIVES: Local excision of rectal carcinoma has primarily been limited to patients with small (< or =3 cm), early rectal carcinoma. We wanted to determine whether local excision (transanal or transacral), when combined with selective chemoradiation therapy, would be adequate treatment for patients with larger (>3 cm) and more advanced T3 and N1 tumors. METHODS: A prospective study of 20 patients with clinical T1-T3, N0-N1 rectal carcinoma was initiated in 1990. Local excision (transanal or transacral) was performed on all patients. Sixteen patients were treated with postoperative 5-fluorouracil (5-FU) and leucovorin (LV) combined with radiation therapy; six high-risk patients (T3 or N1) received an additional 6 months of 5-FU and LV. All patients were followed for a minimum of 4 years. RESULTS: Tumor size ranged from 2 to 5.5 cm (mean, 3.6 cm). Histology revealed well or moderate differentiation (19/20), gross or microscopic ulceration (14/20), and vessel invasion (5/20). Mucosal margins were 3-12 mm (mean, 8.3 mm); radial margins were clear in all patients except one (microscopically positive). Five patients had T3 tumors; two had node positive tumors (N1). With a median follow-up of 56 months (48-71), there have been no local or regional failures and two patients have died from metastatic disease. CONCLUSIONS: Local excision, when combined with selective chemoradiation therapy, can be safely applied to patients with large (>3 cm) and more advanced T3 and N1 rectal carcinomas.     

Radiation therapy for unresectable rectal cancer

The standard approach to patients with unresectable rectal cancer is pre-op radiation therapy followed by surgery. To determine the impact of RT on local failure and survival, we present an analysis of our preliminary results of this approach in patients with unresectable rectal cancer. A total of 22 patients were analyzed (9 primary, 13 recurrent). The median follow-up was 22 months. There were two groups of patients. Group 1 included 12 patients with unresectable tumors in whom surgery was planned following pre-operative radiation therapy. Group 2 included 10 patients in whom no surgery was planned following radiation therapy due to extensive pelvic bone destruction. The whole pelvis received 4680 cGy followed by a boost of 360-1440 cGy. Six underwent brachytherapy. For the total patient group, the 3-year actuarial survival was 52% (Group 1: 91% vs Group 2: 30%). Patterns of failure as a component of failure were: local failure (or local progression): 50%, abdominal: 23%, and distant: 9%. The dose of pelvic radiation had no significant impact on the local failure rate (5040 cGy: 55% vs greater than 5700 cGy:45%). None of the seven patients with negative margins developed local failure compared with 73% of those with positive margins. The complete resection rate in Group 1 patients was 58%, and all are alive without local failure. Further follow-up will be needed to determine the ultimate local failure and survival rates.     

Treatment of locally advanced rectal cancer with external beam radiation, surgical resection, and intraoperative radiation therapy

To try to improve the local control and survival of patients with locally advanced rectal cancer we have used a combination of high-dose pre-operative radiation therapy to 5,040 cGy followed by surgical resection and intraoperative electron beam radiation therapy (IORT) when there was visible or palpable residual disease, microscopically positive surgical margins, or persisting tumor adherence. A total of 75 patients were taken to surgery for resection +/- IORT who did not have distant metastases. Of the 49 patients with primary tumors, 11 did not have IORT as the tumor was thought to be completely resected. Of these 11, there were two local recurrences and a 3-year survival of 71%. Thirty-six patients with primary tumors had resection (20 complete, 16 partial) plus IORT, with a 3-year survival of 58% and three local failures. Twenty-six additional patients were treated for locally advanced recurrence of whom four could not receive IORT because of pelvic size or the extent of tumor. Of the 22 who received IORT, 7/9 with complete resection, 2/8 with partial resection, and 1/5 with no resection had local control with an overall 3-year actuarial survival of 32%. The local control and survival results in the primary tumors appear favorable compared to other series in the literature and suggest benefit to the use of IORT. For patients treated for local recurrence, local control and long-term survival can be obtained, but the results are not as encouraging as for the primary tumors.     

Limb salvage therapy for soft tissue sarcomas of the foot

From 1974 to 1988, 20 patients with soft tissue sarcomas of the foot underwent attempted limb preservation at UCLA. Eighteen patients had localized tumor and two had metastases. Sixteen patients had previously untreated tumors and four patients had experienced 2-4 local recurrences before definitive management. Eleven patients had grade 3 sarcomas and nine had grade 2 sarcomas. Fourteen patients had an excisional biopsy and six had an incisional biopsy. At the time of definitive local treatment, nine patients had palpable tumor ranging from 2-10 cm (median 5 cm). Sixteen patients received sequential preoperative chemotherapy and irradiation followed by attempted conservative resection. Four patients underwent immediate conservative resection followed by postoperative irradiation. Preoperative chemotherapy was administered over 3 days intraarterially, intravenously or by a combination of routes. Fifteen patients received 60-90 mg doxorubicin and one received 120 mg doxorubicin plus 220 mg cisplatinum. Preoperative irradiation was delivered in 350 cGy fractions to total doses of 3500 cGy (one patient), 2800 cGy (8) or 1750 cGy (7). Postoperative irradiation doses were 4140-6480 delivered in 180-200 cGy fractions. Fifteen of 16 preoperatively treated patients had limb salvage surgery. Four of these 15 had positive histopathologic margins and none received postoperative irradiation. One patient required a primary amputation due to gross involvement of the os calcis. Three of four patients undergoing immediate conservative excision had positive margins and one had gross residual disease. Five patients received chemotherapy following local treatment: 3 adjuvantly and 2 for metastatic disease. Follow-up for salvage patients ranged from 6 to 99 months (median 36). Local control was achieved in 17 of 19 (90%). Two patients recurred in-field at 24 and 30 months. Fourteen of 15 preoperatively treated and salvaged patients maintained local control. Three of four managed with excision and postoperative irradiation were controlled. The actuarial local control at 3 years was 83%. One patient recurred in the inguinal lymph nodes and three patients died of metastatic disease. The actuarial survival and relapse-free survival at 3 years were 83% and 63%. Eleven patients developed acute complications and four had late complications. Of 14 patients surviving with local control, function was good or excellent in 86%. No patient has required an amputation for complications or a dysfunctional foot. Limb salvage therapy for a selected patient with a soft tissue sarcoma of the foot can reasonably be expected to result in a high probability of local control and useful function without compromising survival.     

Local therapy for rectal cancer.

In selected patients with early rectal cancer, local therapy is an effective alternative to radical resection and offers minimal morbidity and the avoidance of a colostomy. Several techniques are described: transanal excision, dorsal approaches (York-Mason or Kraske procedures), transanal endoscopic microsurgery, endocavitary radiation, and transanal fulguration. Among these, transanal excision is favored for the low rate of complications, promising outcomes, and ability to secure tissue for pathology. Patients with T1 lesions with favorable histologic features may undergo local excision alone, while those with T2 lesions require adjuvant chemoradiation. The data currently available do not support the use of local therapy with curative intent for tumors that are advanced (T3 or T4), poorly differentiated, or have other negative pathologic characteristics. In carefully selected patients for local excision, local recurrence and survival rates are similar to traditional radical resection. Following local excision, patients require close observation for recurrence. Most patients with local recurrence can be salvaged by radical resection, though the long-term outcome is unknown.     

Conservative management of rectal cancer with local excision and adjuvant therapy

The standard surgical treatment of distal, resectable, invasive rectal cancers is an abdominoperineal resection or a low anterior resection. Given the morbidity associated with these standard treatments and the frequent need for postoperative adjuvant therapy, the use of a more conservative approach, such as local excision with adjuvant therapy as primary therapy for selected cases of rectal cancer is appealing. Data from single-institution series as well as recent data from prospective, multi-institutional studies, suggest that local excision with adjuvant therapy is a reasonable alternative to radical surgery in selected patients. Local excision alone is acceptable treatment only for T1 tumors without adverse pathologic features, while local excision with adjuvant therapy is an alternative treatment for T1 tumors with adverse pathologic features and T2 tumors. Some series suggest that preoperative therapy with local excision may be a possible treatment for selected T3 tumors; however, the high local failure rates seen in T3 tumors treated with local excision and postoperative therapy cautions against this approach. Functional results with local excision are generally good, and postoperative morbidity and mortality is acceptable. In summary, the results of local excision and radiation therapy are encouraging. Randomized trials are needed to determine whether this approach has local control and survival rates comparable to those of radical surgery.     

Intraoperative electron beam radiation therapy for primary locally advanced rectal and rectosigmoid carcinoma

To improve local control and survival in patients with primary locally advanced rectal and rectosigmoid carcinoma, intraoperative electron beam radiation therapy (IORT) has been used with a combination of moderate- to high-dose preoperative radiation therapy and surgical resection. Sixty-five patients underwent resection with the intention of using IORT if areas at high risk for local recurrence were apparent at surgery. For 20 patients undergoing complete resection with IORT, the 5-year actuarial local control and disease-free survival (DFS) was 88% and 53%, respectively. The results for 22 patients with pathologically documented residual carcinoma were less satisfactory with a 5-year actuarial local control and DFS of 60% and 32%, respectively. In this latter group, local control and DFS correlated with the extent of residual disease: patients with only microscopic disease had a 5-year actuarial local control and DFS of 69% and 47%, respectively, whereas for patients with macroscopic disease, these figures were 50% and 17%, respectively. For 18 patients undergoing complete resection without IORT or additional postoperative radiation therapy, the 5-year actuarial local control and DFS was 67% and 53%, respectively. Because local failure will occur in at least 30% of patients undergoing partial resection with or without IORT as well as patients undergoing complete resection of advanced tumors without IORT, additional postoperative radiation therapy should be considered.     

A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience

Between 1976 and 1985, 155 patients from the Hospital of the University of Pennsylvania, the Philadelphia Veterans Administration Hospital, and the Fox Chase Cancer Center were divided into groups, each of which was treated with one of three preoperative radiotherapy regimens to be followed by cystectomy. Patients initially were treated with 4000 cGy during 4 weeks followed by cystectomy (16 patients). Beginning in 1978, patients received 2000 cGy in 1 week prior to surgery (70 patients). Since 1982, 40 patients were treated with 500 cGy on the day prior to surgery with postoperative radiation therapy reserved for patients with either involved margins of resection, advanced stage or high grade. A fourth group of 20 patients was either not offered or refused preoperative radiation. Nine patients received only postoperative radiation therapy. The 5-year actuarial disease-free survival for pathologic Stages B2, C, and D lesions (T3-4, N0-2), was 63% for those who had received high-dose radiation versus 21% for those that had low-dose or no radiation. Patients with advanced pathologic stage disease who had received greater than 2000 cGy had a reduced rate of local failure (11% versus 27% for those who had received less treatment). Patients with abnormal upper tracts as shown on the intravenous pyelograms (IVP) had a reduced 5-year determinate survival of 23% versus 65% for patients with normal upper tracts. This condition did not independently affect survival, but rather reflected advanced stage. Patients with abnormal creatinine levels had a decreased survival that was independent of stage. Computed tomography was found to have low sensitivity for determining extravesical extension (39%) and metastatic lymphadenopathy (12%). Patients with clinical Stage B2 and C disease (T3) that were downstaged had a 63% 5-year survival versus 18% of those that were not downstaged. The incidence of both ureteroenteral strictures and stomal complications was found to be higher in the 2000 cGy group than in those patients treated with the other regimens. The overall incidence of complications in that group was also significantly greater. We conclude that there is a continuing role for adjuvant radiotherapy in invasive bladder carcinoma to improve both pelvic control and survival. The 500 cGy radiotherapy "sandwich" regimen was equal in terms of pelvic control and survival to the other regimens and showed less overall morbidity. The 2000 cGy regimen was associated with the greatest incidence of morbidity and did not substantially improve pelvic control.     

Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma.

BACKGROUND. The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS. Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). RESULTS. The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. CONCLUSIONS. The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.