Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma

Twenty-five patients with locally advanced but resectable adenocarcinoma of the stomach were given concomitant postoperative radiotherapy to the tumor bed and chemotherapy with 5-Fluorouracil (5-FU). Twenty-two of the patients had regional lymph node involvement and seven had residual tumor in the surgical margins. Radiotherapy was delivered to a total dose of 5,000 rads in 7 weeks with a two-week split. 5-FU was given daily the first 3 days of each treatment period and was then continued weekly for a minimum of 1 year. At a median follow-up time of 19 months, 11 patients have relapsed, two locally and nine distally, and all have died. Thirteen patients remain alive, all but one disease-free, for a median of 21 months from diagnosis. One additional patient died of unrelated causes, free of tumor. The actuarial median survival for the whole group stands at 33 months with a projected 5-year survival of 40%. Treatment has been well tolerated.     

口服替吉奥联合三维适形放疗治疗局部晚期胃癌疗效观察

目的:评估口服替吉奥联合三维适形放疗治疗局部晚期胃癌的疗效和安全性。方法:38例局部晚期胃癌患者进入研究,采用口服替吉奥联合同步三维适形放疗方案治疗,替吉奥在放疗开始的第1天口服,剂量为40-60mg/m2,2次/天,连服2周,休息1周。维持替吉奥口服治疗至放疗结束后4周,评价治疗疗效和毒副反应。结果:全部38例患者均完成同步放化疗,其中完全缓解3例,部分缓解26例,稳定4例,疾病进展5例,总有效率为76.3%;患者进食梗阻、疼痛主观症状改善率分别为78.8%、84.6%。全组1年总生存率55.3%,2年总生存率31.5%。主要不良反应是I-III度消化道反应及血液学毒性,经对症支持治疗后好转。结论:口服替吉奥联合三维适形放疗方案治疗局部晚期胃癌可以提高患者生活质量,不良反应可耐受。     

序贯化放疗治疗局部晚期胃癌的临床疗效

目的:观察化疗-放疗-化疗(化-放-化)序贯治疗局部晚期胃癌的临床疗效和毒副反应.方法:2009年1月-2014年10月我科收治的局部晚期胃癌84例,采用同期对照研究,分为化-放-化序贯治疗组(观察组)44例和单纯化疗组(对照组)40例.观察组及对照组均采用DCF(多西他赛、顺铂、5-氟尿嘧啶)或FOLFOX4(5-氟尿嘧啶、奥沙利铂、亚叶酸钙)方案化疗3~4周期,观察组化疗2周期后开始肿瘤累及区域三维适形放疗/调强适形放射治疗(3DCRT/IMRT),放疗剂量DT(45~50.4)Gy/[(25~28)f?(5~6)w],放疗结束再予相同方案化疗1~2周期.对照组不予放疗.结果:84例患者均可评价疗效,观察组与对照组总有效率(CR+PR)分别为65.9%、37.5%,疾病控制率(CR+PR+SD)分别为88.6%、60.0%,临床症状缓解率分别为88.6%、65.0%,中位生存期分别为12.0个月、10.0个月,1、2年生存率分别为56.8% vs 32.5%、18.2% vs 7.5%.两组比较,在治疗有效率、疾病控制率、临床症状缓解率、中位生存期、1年生存率方面观察组高于对照组,差异具有统计学意义;2年生存率观察组较对照组有增高,但无统计学差异.两组Ⅲ-Ⅳ度骨髓抑制、胃肠道反应、肝肾功能受损发生率相近.结论:序贯化放疗较单纯化疗提高了局部晚期胃癌的治疗有效率,明显缓解患者的临床症状,且使部分患者改善了生存质量,延长生存期,并未增加治疗毒副反应,是不能手术局部晚期胃癌的较好治疗方案.     

Comparison of Effects of Hemoglobin Levels Upon Tumor Response among Cervical Carcinoma Patients Undergoing Accelerated Hyperfractionated Radiotherapy versus Cisplatin Chemoradiotherapy

Purpose: Blood hemoglobin levels are known to influence response to radiotherapy. This retrospectiveanalysis compared the effect of hemoglobin levels upon response to radiation among patients treated withradiation alone (by accelerated hyperfractionated radiotherapy) versus those treated with concurrent cisplatinchemoradiotherapy. Materials and Methods: Among patients treated for locally advanced carcinoma of thecervix (LACC) during 2009-10, a total of 60 fulfilled the eligibility criteria. In this time frame, external beamradiotherapy was delivered with either concurrent chemoradiotherapy (CRT, n=31) (45Gy over 25 fractions,with weekly cisplatin at 40mg/m2), or with accelerated hyperfractionated radiotherapy (AHRT, n=29) (20Gyover 10 daily fractions over the first two weeks, followed by 30Gy over 20 fractions over the next two weeks,with two fractions of 1.5Gy per day, without the use of chemotherapy). Mean weekly hemoglobin (MWH) levelsof all patients were calculated as the arithmetic means of weekly recorded blood hemoglobin levels. As perMWH, patients in both of the AHRT or the CRT groups were classified into two subgroups- those with MWHbetween 10-10.9g/dL, or with MWH>11g/dL. Complete response (CR) to external beam RT phase (prior tobrachytherapy) was declared after clinical examinations and computed tomography. The CR rate was noted forboth MWH sub-groups within each of the AHRT and CRT groups. Results: Within the AHRT group, patientswith MWH>11g/dL had a much better CR rate in comparison to those with MWH:10-10.9g/dL (80% vs. 21.1%)which was statistically significant (p 0.0045). Within the CRT group, there was no significant difference in theoutcomes within the MWH>11g/dL and MWH:10-10.9g/dL sub-groups ( CR rates of 80% vs. 61.9%, p=0.4285).Conclusions: The importance of maintaining a minimum hemoglobin level of 11g/dL during RT is much greaterfor patients treated with RT alone, than for patients treated with concurrent chemoradiotherapy. Enhancedhaemoglobin levels during RT may to an extent negate the ill-effects that may otherwise arise due to non-use ofconcurrent chemotherapy.     

The GOFURTGO Study: AGITG phase II study of fixed dose rate gemcitabine-oxaliplatin integrated with concomitant 5FU and 3-D conformal radiotherapy for the treatment of localised pancreatic cancer

Background:

Locally advanced inoperable pancreatic cancer (LAPC) has a poor prognosis. By increasing intensity of systemic therapy combined with an established safe chemoradiation technique, our intention was to enhance the outcomes of LAPC. In preparation for phase III evaluation, the feasibility and efficacy of our candidate regimen gemcitabine–oxaliplatin chemotherapy with sandwich 5-fluorouracil (5FU) and three-dimensional conformal radiotherapy (3DCRT) needs to be established.

Methods:

A total of 48 patients with inoperable LAPC without metastases were given gemcitabine (1000 mg m⁻² d1 + d15 q28) and oxaliplatin (100 mg m⁻² d2 + d16 q28) in induction (one cycle) and consolidation (three cycles), and 5FU 200 mg m⁻² per day over 6 weeks during 3DCRT 54 Gy.

Results:

Median duration of sustained local control (LC) was 15.8 months, progression-free survival (PFS) was 11.0 months, and overall survival was 15.7 months. Survival rates for 1, 2, and 3 years were 70.2%, 21.3%, and 12.8%, respectively. Global quality of life did not significantly decline from baseline during treatment, which was associated with modest treatment-related toxicity.

Conclusion:

Fixed-dose gemcitabine and oxaliplatin, combined with an effective and safe regimen of 5FU and 3DCRT radiotherapy, was feasible and reasonably tolerated. The observed improved duration of LC and PFS with more intensive therapy over previous trials may be due to patient selection, but suggest that further evaluation in phase III trials is warranted.     

淋巴结清扫范围对进展期胃癌患者预后的影响研究

目的探讨不同淋巴结清扫方案对进展期胃癌患者预后的影响。方法选取267例进展期胃癌患者,所有患者均接受D1或D2淋巴结清扫术。分析淋巴结转移与进展期胃癌患者临床特征的关系,并对不同淋巴结清扫术后胃癌患者的生存情况进行分析。结果不同性别、年龄、肿瘤部位进展期胃癌患者的淋巴结转移率比较,差异均无统计学意义(P>0.05);不同肿瘤最大径、Borrmann分型、TNM分期、分化程度进展期胃癌患者的淋巴结转移率比较,差异均有统计学意义(P<0.05)。行D2淋巴结清扫术的进展期胃癌患者的中位生存时间为55.0个月(95%CI:51.1～58.9),明显长于行D1淋巴结清扫术患者的28.5个月(95%CI:21.3～34.7)(P<0.01)。结论肿瘤最大径、Borrmann分型、TNM分期及分化程度可能影响进展期胃癌患者的淋巴结转移情况,而D2淋巴结清扫术后进展期胃癌患者能获得更长的生存期。     

The effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy

EROGLU C., ORHAN O., KARACA H., UNAL D., DIKILITAS M., OZKAN M. & KAPLAN B. (2013) European Journal of Cancer Care 22 , 133–140 The effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy The aim of this study was to examine the effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy and chemotherapy. In this study 152 patients were evaluated. Radiotherapy dose was 45 Gy given in 5 weeks. 5-FU 425 mg/m² and folinic acid 20 mg/m² were administered weekly during the radiotherapy and four cycles with 4-week intervals as consolidation chemotherapy after radiotherapy. Patients were assigned into two groups according to their body mass index: overweight (body mass index ≥25 kg/m²) and normal weight (body mass index <25.0 kg/m²). The median overall survival was 39 months vs. 18 months and median disease-free survival was 27 months vs. 13 months in the overweight and normal-weight groups respectively (P= 0.004 and P= 0.006 respectively). The 5-year survival was better in the patients with overweight than those with normal weight (42% vs. 17%; P= 0.004). The overall survival was significantly better with being overweight and early pathological stage (P= 0.016 and P= 0001 respectively). Overall survival, disease-free survival and long-term survival in patients with gastric cancer undergoing adjuvant treatment were better in overweight than normal-weight patients. Moreover, it was shown that body mass index and pathological stage were associated to survival and prognosis.     

局部晚期胃癌根治术后放射治疗研究进展

术后同步放化疗是局部晚期胃癌根治术后重要的辅助治疗手段。对于局部晚期胃癌根治术后淋巴结清扫小于D 2 范围者,术后同步放化疗可以提高局部和长期的疗效,为指南推荐的术后辅助治疗标准方案。D 2 术后是否需同步放化疗仍存在争议。来自亚洲的3 项Ⅲ期随机分组临床试验表明D 2 术后同步放化疗安全可行并可能使部分患者获益;术后同步放化疗的作用仍需设计良好、检验效率充分的随机对照临床试验进一步明确。下一步研究的重点将侧重于筛选可从同步放化疗中获益的局部区域复发高危人群、进一步优化放疗靶区范围、探索应用新的放疗技术等方面。      

The ODAC Chronicles: Part 5. Prostate cancer endpoints

Head and neck cancer management has undergone several paradigm shifts for several relevant reasons. From the dismal experience with the use of radiotherapy as the sole modality in the treatment of this group of patients with advanced disease, radiotherapy has been evaluated as an adjuvant for the same group of patients who had undergone successful surgery. Although there is no level 1 evidence to support postoperative adjuvant radiation, several studies have demonstrated that adjuvant radiotherapy reduces the local failures and, thereby, improves survival. Predictors of recurrence after surgical resection are: positive margins of resection; extranodal spread in involved nodes; perineural invasion; and presence of two or more involved regional lymph nodes. Realization of the advantages of a combination of chemotherapy with radiotherapy has had a major impact on the management of these cancers. There is emerging evidence for the use of adjuvant concurrent chemoradiotherapy in the group with high-risk features. Multiple organ conservation strategies in the management of locally advanced head and neck cancers have evolved over the years. However, the meta-analyses of impact of chemotherapy in various settings reveal that concomitant chemoradiotherapy is superior to any of the other regimens. Increasing use of computed tomography, magnetic resonance imaging and positron emission tomography scan images has resulted in better visualization of target volumes and critical structures. Delineation of these structures is of paramount importance and has resulted in a profound change in conformal treatment planning. Better understanding of the physical aspects of delivery of radiotherapy and the advent of modern treatment planning systems have led to the development of conformal techniques. Although the benefit of these techniques on survival have yet to be demonstrated, there is evidence to suggest that they reduce treatment-related toxicities significantly and facilitate dose escalation. Increased knowledge of radiobiology has led to the development of various altered fractionation regimens in the management of locally advanced head and neck cancers. Discovery of cell-cycle kinetics and signal transduction pathways has led to the unearthing of several potential targets for targeted therapy. The epidermal growth factor recepter gene has emerged as the most promising target. The role of biological radiation response modifiers is evolving. All of these approaches to improve the therapeutic gain would be incomplete without evaluating their effect on the quality of life of these patients.     

术后辅助放化疗与单纯手术治疗在胃腺癌中的比较

Objective:Despite resection with curative intent,a majority of patients with gastric cancer will develop disease recurrence.Postoperative adjuvant chemo-radiotherapy increase the curability of surgery,prevent local recurrence and improve survival.Methods:Between December 2005 and February 2010,33 patients were eligible for the study,17 patients were randomly assigned for chemo-radiotherapy (GI) and 16 patients with surgery alone (GII).Patients in GI received chemotherapy (fluorouracil,425 mg/m 2/day,and leu...     

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy

AimsThere are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy.Materials and methodsPatients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4–6 Gy sequential boost for nodes >2 cm.ResultsOf the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9–46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%).ConclusionThis is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.     

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.     

Evaluation of the toxicity of the combined treatment of chemoradiotherapy, according to the scheme of Macdonald, after radical surgery in patients diagnosed of gastric cancer

Purpose In this study we evaluated the acute toxicity of the combined treatment with chemoradiotherapy, according to the scheme of McDonald et al, in patients diagnosed with gastric cancer, after radical curative surgery. Methods From July 2001 to December 2005, a total of 24 patients, with diagnosis of adenocarcinoma of the stomach or adenocarcinoma of the gastroesophageal junction, who were operated with total or subtotal gastrectomy with free resection margins, were treated at our service with a combined scheme of adjuvant chemoradiotherapy. Results p Grade 3 toxicity or higher appeared in three patients (12%) and grade 2 in five of the twenty-four patients (21%). Two patients (8%) needed to suspend treatment before the scheduled end date of treatment due to acute toxicity. No acute toxicity of cardiological, hepatic or renal nature was registered, and the most frequent toxicity was the gastrointestinal toxicity (detected in the 79% of the patients). Conclusions Combined treatment with chemoradiotherapy, according to the scheme of Macdonald, in diagnosed patients with gastric cancer, after radical curative surgery is a well tolerated treatment, with a low degree of acute toxicity, thus the treatment compliance is not difficult.     

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: a large population-based study

BACKGROUND:

Significant improvements in the survival of women with breast cancer have been observed and are attributed to a multidisciplinary approach and the introduction of polychemotherapy and endocrine regimens. The objective of this population‐based study was to determine whether women with inflammatory breast cancer (IBC) who received treatment in a modern era had a poorer survival compared those with non‐IBC locally advanced breast cancer (LABC).

METHODS:

The Surveillance, Epidemiology, and End Results program registry was searched to identify women with stage IIIB/C breast cancer diagnosed between 2004 and 2007 who had undergone surgery and radiotherapy. Patients were categorized as either having IBC or non‐IBC LABC according the sixth edition of the American Joint Committee on Cancer (AJCC) criteria. Breast cancer‐specific survival (BCS) was estimated using the Kaplan‐Meier product limit method and compared across groups using the log‐rank statistic. Cox models were then fitted to compare the association between breast cancer type and BCS after adjusting for patient and tumor characteristics.

RESULTS:

A total of 828 (19.2%) women and 3476 (80.8%) women had stage IIIB/C IBC and non‐IBC LABC, respectively. The median follow‐up was 19 months. The 2‐year BCS rate was 90% (95% confidence interval [95% CI], 88%‐91%) for the entire cohort and 84% (95%CI, 80%‐87%) and 91% (95%CI, 90%‐91%) among women with IBC and non‐IBC LABC, respectively. In the multivariable model, patients with IBC were found to have a 43% increased risk of death from breast cancer compared with patients with non‐IBC LABC (hazard ratio, 1.43; 95%CI, 1.10‐1.86 [P = .008]).

CONCLUSIONS:

In the era of multidisciplinary management and anthracycline‐based and taxane‐based polychemotherapy regimens, women with IBC continue to have worse survival outcomes compared with those with non‐IBC LABC. Cancer 2011. © 2010 American Cancer Society.