Intra-arterial infusion chemotherapy as preoperative treatment of locally advanced breast cancer.

Intra-arterial infusion chemotherapy was made through the internal mammary artery and subclavian artery in 12 cases of locally advanced breast cancer. Continuous infusion of 5-fluorouracil and intermittent injections of Mitomycin C were jointly made for 1 to 4 weeks in each artery. Marked response in not only the primary tumor but also lymph node metastasis was clinically observed, permitting extended radical mastectomy successfully in all cases. Remarkable regressive changes were histologically observed in cancer foci, especially in small ones, of resected specimens including axillary, parasternal, and supraclavicular lymph nodes. All cases except 1 have been healthy without any recurrence for 22 to 78 months after treatment. Intra-arterial infusion chemotherapy will this method is a useful preliminary procedure for surgical treatment of locally advanced breast cancer.     

Summated chemotherapy dose-intensity versus loco-regional response in locally advanced breast cancer: its possible implications

BACKGROUND: Summated dose-intensity (SDI) of chemotherapy regimen could influence the outcome in malignancies. AIMS: To evaluate the implication of SDI and identify key drugs for loco-regional response in locally advanced breast cancer (LABC). Settings and design: This retrospective study was based on audit of records of LABC patients who had received neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: Actual unit dose-intensity (UDI) of each drug and corresponding SDI of every doxorubicin (n=116 cycles) or non-doxorubicin (n=110 cycles) based NACT received by 42 patients of LABC were summated. Cumulative dose-intensity (CDI) for individual drugs and cumulative SDI (CSDI) for the entire course of NACT were estimated and correlated with quantum of primary tumor, axillary and supraclavicular nodal responses. STATISTICAL ANALYSIS USED: Two-sided chi-square, t-test, step-wise regression was used. RESULTS: Dose-response curve between CSDI and corresponding responses for both primary and lymph nodes were sigmoid in shape for both doxorubicin or non-doxorubicin based NACT. Curves were best fitted using a cubic fit for all patients (r2 = 0.82, 0.84 and 0.93 for primary tumor, axillary and supraclavicular lymph nodes respectively). CSDI emerged as an important prognosticators for both primary (P<0.001) and nodal (P<0.001) responses. Individually, CDI of 5-fluorouracil for primary (P<0.001), CDIs of doxorubicin (P<0.001) and methotrexate (P=0.006) for axillary nodes and CDI of cyclophosphamide (P=0.001) for supraclavicular nodes were significant. CONCLUSIONS: Loco-regional responses in LABC are dependent on CSDI of NACT regimen. Drugs for high-dose intensification protocols could be identified and chosen based on the impact of CDI of individual drugs in NACT.     

Dose-intensive chemotherapy for locally advanced breast cancer

The availability of hematopoietic growth factors has allowed a range of feasibility and uncontrolled studies with high-dose chemotherapy (with or without stem-cell support) to take place. Preliminary data from some randomized studies are now available as well. Dose-intensive chemotherapy appears to be effective in downstaging the tumor. Only a minority of patients achieve a pathologic complete remission and additional therapeutic options to control minimal residual disease are urgently needed. There are few indications that highdose chemotherapy is superior to conventional dose therapy in terms of relapse-free or overall survival. Although the results of most randomized studies are premature or unknown at this time, a modest but clinically significant survival advantage may still emerge.     

Neoadjuvant chemotherapy in locally advanced breast cancer

Thirty-eight patients with locally advanced breast cancer (Stage III) were treated over a 3-year period. All patients initially received two cycles of CMF (cyclophosphamide, 100 mg/m² p.o. d1–14; methotrexate 40mg/m² intravenously (iv), d1 and d8., 5 Fluorouracil 500 mg/m² iv d1 and d8). They were then subjected to surgery and external beam irradiation to the chest field and drainage areas. Four more cycles of chemotherapy completed the treatment protocol. A response to initial chemotherapy was seen in 75.7% patients, with two patients achieving a complete response. No patient had disease progression while on chemotherapy. Tumor reduction of a degree to allow breast conservation procedures was seen in eight patients. The chemotherapy was well tolerated. Twelve patients failed to complete the treatment protocol. Follow-up for the remaining 26 ranges from 9–40 months (mean 18 months). Ten patients developed a recurrence. Of those, only one had isolated local recurrence, two had local and systemic recurrence, and seven had systemic disease alone. Patients with recurrence were salvaged with further chemotherapy (Adriamycin and cyclophosphamide). © 1996 Wiley-Liss, Inc.     

新辅助化疗对局部晚期乳腺癌术后局部复发的影响

目的探讨新辅助化疗对局部晚期乳腺癌术后局部复发的影响。方法将我院1995年1月至2000年1月间完成术后系统治疗的128例局部晚期乳腺癌病例,根据是否新辅助化疗分为A(行新辅助化疗组)、B(未行新辅助化疗组)两组对照,通过总结两组的复发情况,分析新辅助化疗对局部晚期乳腺癌术后局部复发的影响。结果A组69例中有9例复发,复发率13.0%;B组59例中有20例复发,复发率33.9%,两组复发率差异有显著性(P<0.05)。A组复发者中多为单发,便于复发后的再治疗。结论CTF方案术前新辅助化疗可以降低局部晚期乳腺癌的术后局部复发率。     

The surgical management of patients following neoadjuvant chemotherapy for locally advanced breast cancer

The aim of this study was to evaluate the role of surgery in patients who achieve a complete clinical response (cCR) to neoadjuvant chemotherapy for locally advanced breast cancer. A retrospective study of patients with either large central (T2 >30 mm, N0 or N1, M0) or locally advanced (T3, N0 or N1, M0) tumours who received neoadjuvant chemotherapy followed by surgery to the breast and axilla and postoperative radiotherapy. All patients had operable disease at presentation. A total of 133 patients were included. Overall, 43 (32%) patients achieved a cCR following chemotherapy. Of these, 19 patients had no pathological evidence of disease in the breast (pCR) or on imaging or core biopsy and these patients received only adjuvant radiotherapy to the breast. A further 5 patients had no pathological evidence of cancer following breast surgery. 126 patients had an axillary clearance. Increasing response to chemotherapy was related to fewer pathologically involved nodes, but 7 of 24 (29%) patients with a pCR still had evidence of axillary metastases. This is the principal conclusion of the study at the present time. The patients were followed-up for a median of 30 months (range 5–83 months) with a local recurrence rate of 3.8%. There was no difference in either distant recurrence-free or overall survival between patients experiencing a pCR and the remainder.     

MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy

Purpose

To evaluate a simultaneous integrated boost (SIB) strategy in preoperative radiotherapy of rectal cancer patients following neoadjuvant chemotherapy using pre- and post-chemotherapy tumor volumes assessed by MRI.

Materials and methods

Ten patients with locally advanced rectal cancer, receiving chemotherapy prior to radiotherapy, were included in this study. Pre- and post-chemotherapy MR tumor images were co-registered with CT images for IMRT planning. Three planning target volumes were defined: PTV_risk, PTV_{pre_chemo} and PTV_{post_chemo}. For SIB, prescribed mean doses to the PTVs were 46, 50 and 58 Gy, respectively, given in 25 fractions. Organs at risk (OARs) were bladder and intestine. The novel three-volume SIB strategy was compared to a conventional two-volume SIB plan, in which PTV_{post_chemo} was ignored, using dose-volume histograms (DVHs) and the generalized equivalent uniform dose (gEUD).

Results

All patients showed tumor shrinkage following chemotherapy. For the novel SIB, population-based mean doses given to PTV_risk, PTV_{pre_chemo} and PTV_{post_chemo} were 46.8 ± 0.3, 50.6 ± 0.4 and 58.1 ± 0.4 Gy, respectively. DVHs and gEUDs for PTV_risk, PTV_{pre_chemo}, bladder and intestine revealed minimal differences between the two SIB strategies.

Conclusions

Tumor volume reduction for rectal cancer patients following neoadjuvant chemotherapy allows for increased tumor dose using a SIB strategy without increased OAR toxicity.     

Neoadjuvant chemotherapy FEC-HD in locally advanced breast cancer

The tolerance and the clinical and histological efficacy of a neoadjuvant chemotherapy FEC-HD including hematopoietic growth factors have been studied in 40 patients with stade II or III breast cancer between February 1991 and February 1997. Four courses were given, every 21 days, with 5-fluorouracil (750 mg/m2/day D1 to D4 by continuous infusion), epirubicin (35 mg/m2/day D2 to D4) and cyclophosphamide (400 mg/m2/day D2 to D4) with G-CSF (5 mug/kg/day D6 to D15). The surgery was performed 3 or 4 weeks after the end of the chemotherapy. All patients had radiotherapy. The neoadjuvant chemotherapy induced 37.5% CR, 45% PR, and 15% SD. In 40% of the patients, the surgery was conservative. An histological CR was obtained in 15% with no axillary involvement one time out of two. There was intraductal carcinoma without invasive carcinoma in 7.5%. There was no differences between the response of inflammatory and non inflammatory tumors. One hundred and fifty-eight courses have been delivered. A grade 3 or 4 leuconeutropenia, anemia and thrombopenia have been observed in respectively 34.6%, 6.3% and 8.8% of the courses. A grade 3 or 4 mucositis has been noticed in 2.5% of the courses. A febrile granulocytopenia has occurred in 3.8% of the courses. The median survival without metastatic progression was 48 months and the median overall survival was not achieved. In stade II and III breast cancer, neoadjuvant chemotherapy with FEC-HD obtains an important histological response with an acceptable toxicity. The role of the dose-intensity increase on survival remains to be determined.     

新辅助化疗治疗局部进展期乳腺癌的临床观察

目的 探讨新辅助化疗用于局部进展期乳腺癌的临床价值.方法 选取1996年1月至2006年12月经病理确诊的局部进展期乳腺癌522例,随机分为新辅助化疗组264例和对照组258例.新辅助化疗组给予FEC或TEC方案化疗4～6周期后进行手术,符合保乳条件者实施保乳手术;对照组实施全乳房切除术.分析新辅助化疗对局部进展期乳腺癌保乳率以及预后的影响.结果 新辅助化疗组总有效率为89.19%(231/259),82.20%(217/264)的患者达到保乳条件,其中实际实施保乳手术85例.经67.4(36～166)个月随访,新辅助化疗组的复发率、转移率、总生存率及无病生存率与对照组相比,差异均无统计学意义(P＞0.05);临床完全缓解者的总生存率和无病生存率分别为92.64%(63/68)、88.23%(60/68),高于未达到临床完全缓解者的81.15%(155/191)、73.82%(141/191),差异有统计学意义(P=0.026;P=0.017);病理完全缓解的35例患者OS、DFS分别为97.14%(34/35)、94.19%(33/35),未达到病理完全缓解的224例患者OS、DFS分别为81.25%(182/224)、75%(168/224),差异均有统计学意义(P=0.019;P=0.015).结论 新辅助化疗可以使局部进展期乳腺癌的原发肿瘤缩小,提高保乳率,准确地进行治疗前分期将是判断新辅助化疗对该癌预后影响的关键.     

局部进展期胃癌术前化疗与术前放化疗的对比研究

背景与目的：术前化疗和术前放化疗都是胃癌治疗指南推荐的针对局部进展期胃癌患者的治疗方法。然而,由于缺乏对比性的研究证据,两者的优劣性不详。本研究将对比术前放化疗与术前化疗在临床疗效及毒性反应之间的差异。方法：2007年6月—2012年10月期间,30例局部进展期胃癌患者入组一项术前化疗的Ⅱ期临床试验,采用EOF（表柔比星+奥沙利铂+氟尿嘧啶）方案进行3~4个周期的术前化疗,对于能手术的患者予以手术,术后给于2~3个周期的EOF方案化疗。2012年4月—2014年8月,40例局部晚期胃癌患者入组一项术前放化疗的Ⅱ期临床试验,患者接受1个周期的SOX［替吉奥（S-1）+奥沙利铂］方案化疗,继续行同步放化疗,再进行1个周期的SOX方案化疗,对于能手术的患者予以手术,术后给于4个周期的SOX方案化疗。比较两项临床试验患者的临床病理特点、术前治疗的效果、R0手术切除率、预后及不良反应。结果：术前化疗临床试验定义为化疗组,有30例胃癌患者入组,且完成了所有的术前化疗,都可评估。术前放化疗临床试验定义为放化疗组,有40例胃癌患者入组,其中36例（90%）患者可评估。两组间的基线参数,如性别、年龄、美国东部肿瘤协作组（Eastern Cooperative Oncology Group,ECOG）评分、临床T分期、临床N分期及肿瘤部位,差异无统计学意义。化疗组的临床有效率（CR+PR）为30%（9/30）,放化疗组的临床有效率（CR+PR）为41.7%,两者间的差异无统计学意义（P>0.05）。化疗组与放化疗组间的R0手术切除率差异无统计学意义（46.7% vs 66.7%）。放化疗组的病理有效率高于化疗组,且差异有统计学意义（50.0% vs 23.3%）。术前放化疗组的毒性反应较化疗组明显。放化疗组的3年总生存率为41%,高于化疗组的20% （P=0.009）。结论：放化疗组的病理有效率及3年总生存率高于化疗组。急性毒性反应也较化疗组明显,但无严重的毒性反应。     

Prognostic factors in locally advanced noninflammatory breast cancer. Long-term results following primary chemotherapy

Since 1973 we have treated T3b-T4 (stage III) breast cancer with various forms of multidisciplinary approaches through prospective trials. The present report analyses the 10-year results of 277 patients. Primary chemotherapy consisted of adriamycin plus vincristine given for three or four cycles prior to high-energy irradiation or surgery. In 205 of 277 (74%) additional chemotherapy was planned following the local-regional modality. Primary chemotherapy yielded complete plus partial remission in 62% (CR 7%). Long-term freedom from progression and overall survival were significantly improved by the addition of chemotherapy following local-regional treatment (radiotherapy or surgery). Further chemotherapy was able to significantly affect treatment outcome when it was analyzed both singly and in the presence of other prognostic variables. Thus, in our experience, the variables significantly affecting the 10-year results were represented by duration of treatment and tumor cell burden expressed by size of primary malignancy and clinical nodal status. Locally advanced breast cancer appears a pleomorphic disease difficult to control over a long period of time because of its frequent presentation with bulky tumor and the very high risk of disseminated micrometastases. Thus, the management of this stage of disease almost invariably requires a multidisciplinary approach.     

局部晚期宫颈癌术前新辅助化疗的疗效分析

目的 探讨术前新辅助化疗治疗局部晚期宫颈癌的临床疗效.方法 回顾性分析78例局部晚期宫颈癌患者的临床资料,根据治疗方式的不同将患者分为研究组(n=48)和对照组(n=30).研究组患者新辅助化疗后接受手术或者放疗,对照组患者直接接受手术治疗.观察研究组患者的近期疗效,比较两组患者的手术情况、术后病理结果及生存情况.结果 治疗后研究组48例患者中,5例(10.42%)患者达到完全缓解,34例(70.83%)患者达到部分缓解,7例(14.58%)患者为疾病稳定,2例(4.17%)患者为疾病进展,有效率为81.25%(39/48).两组患者的手术时间和术中出血量比较,差异均无统计学意义(P﹥0.05).两组患者的手术并发症均较少,研究组中1例患者术后出现肠梗阻、败血症,对照组中3例患者术后出现腹壁切口愈合不良,1例患者术后出现输尿管阴道瘘.术后,研究组和对照组患者的淋巴脉管浸润率分别为24.44%和40.00%,3年生存率分别为85.4%和73.3%,差异均无统计学意义(P﹥0.05).结论 术前新辅助化疗对局部晚期宫颈癌患者具有较好的疗效,为宫颈癌根治术创造了条件,且不增加手术难度和术后并发症,对术后总生存率无明显影响,是治疗该类疾病的一种有效的辅助治疗手段.     

Four cases of locally advanced colorectal cancer resected successfully after preoperative chemotherapy

We describe four cases of locally advanced colorectal cancer resected successfully after preoperative chemotherapy conducted between April of 2007 and April of 2009. The average age of the patients was 66.3 years (range, 40-77 years). Because of tumor invasion into the surrounding organs, preoperative chemotherapy with FOLFOX4 was performed. The average number of courses of chemotherapy was 5.2 (range, 4-7). After chemotherapy, we were able to perform radical operations for all four cases. Histopathological examination of the tumor revealed Grade 3 in one case. There were no postoperative complications and no recurrences in any of the cases. We performed curative surgery after chemotherapy, and good results were obtained. Preoperative chemotherapy may be effective for avoiding excessive intervention surgeries such as total pelvic exenteration, preserving bladder and rectal functions, and for maintening QOL.     

Preoperative chemotherapy followed by mastectomy for locally advanced breast cancer

Six patients with advanced local-regional breast cancer were reviewed. Five out of the six patients previously had had radiation therapy as part of the initial therapy. All patients had preoperative cycles of combination chemotherapy, either CMF or CAF. The two stage III patients had greater than 75% reduction in measurable tumor mass, which allowed a conventional modified radical or radical mastectomy to be performed. Both of these patients are now disease free at 26 and 27 months. The four stage IV patients had lesser operations following the chemotherapy (two simple mastectomies, one simple mastectomy plus axillary resection, and one axillary debulking). Reconstruction utilized advancement flaps in three patients and split-thickness skin grafts in the other. None of the patients had postoperative wound problems, and none of the patients had further problems with local cancer control. All patients had combination chemotherapy starting two to six weeks following surgery. Preoperative chemotherapy followed by surgery plays an important role in management of locally advanced stage III and stage IV breast cancer.     

Intraarterial induction chemotherapy in locally advanced stage III breast cancer

Five-year results are reported on 27 patients with locally advanced breast cancer treated by intraarterial induction chemotherapy followed by radiotherapy and/or surgery with subsequent adjuvant chemotherapy. The cyclic infusion chemotherapy regimen was given over 3 to 6 weeks using Adriamycin (doxorubicin), 5-fluorouracil (5-FU), vincristine, and methotrexate in daily rotation. Regional and systemic side effects were minimal and temporary except in two patients in whom some skin discoloration has remained. Local tumor control and 5-year cures depended on two important factors: whether follow-up mastectomy was used after initial local tumor regression; and whether the carcinoma was classified as "inflammatory" with pathologic evidence of tumor invasion of dermal lymphatics. Of 16 patients with noninflammatory carcinoma treated by chemotherapy, radiotherapy, and mastectomy local tumor eradication was achieved in 15 and 5-year apparent cure in 11. Of six patients with noninflammatory carcinoma treated with chemotherapy and radiotherapy but no mastectomy 5-year local control was achieved in only three and 5-year apparent cure in three. Of five patients with pathologic inflammatory carcinoma local tumor control was achieved in only one and only this one patient has been a 5-year survivor apparently tumor-free.     

Effect of preoperative intra-arterial infusion of adriamycin on locally advanced breast cancer

The effect of adriamycin (ADM) infused intraarterially as a preoperative procedure was analyzed retrospectively in 15 patients with primary advanced breast cancer. A high clinical response rate (CR+ PR) of 73% (11/15) was obtained by the treatment, and also remarkable degenerative changes of tumor cells were histologically noted in 10 out of 15 surgical specimens (67%). A correlation between the dose of ADM infused and the rate of tumor regression was observed. A significantly higher concentration of ADM was detected in metastatic lymph nodes and tumors obtained 3-4 weeks after intra-arterial infusion of ADM than that in normal mammary gland. As for side effects, alopecia, leukocytopenia, anorexia, nausea and vomiting occurred at high frequencies. The side effects due to this treatment were considered to be tolerable. Prognostically, a good survival rate was not observed using preoperative treatment with intra-arterial ADM infusion.     

Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer

The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate.