Comparison of concurrent chemoradiation therapy with weekly cisplatin versus monthly fluorouracil plus cisplatin in FIGO stage IIB-IVA cervical cancer

Objective

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. Although the optimal chemotherapeutic regimen is not yet defined, previous randomized trials have demonstrated that 5-fluorouracil (5-FU) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens. The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer.

Methods

We retrospectively reviewed data from 255 patients with FIGO stage IIB-IVA cervical cancer. Patients were classified into two CCRT groups according to the concurrent chemotherapy: weekly CCRT group, consisted of CCRT with weekly cisplatin for six cycles; and monthly CCRT group, consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen.

Results

Of 255 patients, 152 (59.6%) patients received weekly CCRT and 103 (40.4%) received monthly CCRT. The mean follow-up period was 39 months (range, 1 to 186 months). Planned CCRT was given to 130 (85.5%) patients in weekly CCRT group and 84 (81.6%) patients in monthly CCRT group, respectively. Severe adverse effects were more common in the monthly CCRT group than in the weekly CCRT group. There were no statistically significant differences in progression-free survival and overall survival between the two groups (p=0.715 and p=0.237).

Conclusion

Both weekly CCRT and monthly CCRT seem to have similar efficacy for patients with locally advanced cervical cancer, but the weekly cisplatin is better tolerated.     

Lack of benefit of concurrent chemotherapy in patients with cervical cancer and negative lymph nodes by FDG-PET

PURPOSE: To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. METHODS AND MATERIALS: This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. RESULTS: The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. CONCLUSION: Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET.     

Concurrent weekly cisplatin and radiotherapy in routine management of cervical cancer: a report on patient compliance and acute toxicity

PURPOSE: To evaluate patient compliance and acute toxicity accompanying concurrent weekly cisplatin and radiotherapy (RT) in the routine management of cervical cancer. METHODS AND MATERIALS: Locally advanced or high-risk early-stage cervical cancer patients treated with RT and concurrent weekly cisplatin at a dose of 40 mg/m(2) i.v. (maximum dose, 70 mg) for five cycles. Definitive RT included whole pelvis external beam RT to the International Commission on Radiation Units and Measurements reference dose of 40 Gy plus a 10-Gy boost to the parametrium and two brachytherapy applications of 20 Gy to point A each. Postoperative RT consisted of pelvic external beam RT to the International Commission on Radiation Units and Measurements reference dose of 50 Gy and one brachytherapy application of 30 Gy at a depth of 0.5 cm from the applicator surface. RESULTS: Included in this analysis were 112 consecutive cervical cancer patients treated at one institution with concurrent cisplatin and RT between May 1999 and September 2002. The median age was 48 years (range, 28-79 years). Definitive RT was administered to 57 International Federation of Gynecology and Obstetrics "bulky" Stage IB or IIB-IVA patients, and 53 patients underwent postoperative RT; 2 patients underwent RT for stump carcinoma. All but 2 patients (both administered definitive RT) completed RT. A total of 454 cisplatin cycles were administered (median 4 cycles/patient, range 1-6). Overall, 74% of patients received at least four cycles of cisplatin. The planned five cisplatin cycles were administered to 50 patients (45%); 42% were irradiated definitively and 47% postoperatively. The full and timely planned cisplatin dose was administered to 29 patients (26%). For 29% of patients, the interval between cycles was prolonged because of toxicity (n = 11; 10%) or for reasons not related to toxicity (n = 10; 9%). Of the 112 patients, 62 (55%) did not undergo the planned five cycles of cisplatin because of treatment toxicity (n = 35; 31%) or noncompliance with the treatment schedule because of delayed administration of the first cycle or omission of a cycle for reasons other than toxicity (n = 23; 21%). The most common side effects resulting in chemotherapy discontinuation included GI complications (n = 7) and impaired renal function (n = 5). Of the 112 patients, 49 (44%) experienced Grade 1 or 2 leukopenia and 6 (5%) Grade 3 or 4 leukopenia. CONCLUSION: Our results show that pelvic RT combined with weekly cisplatin in cervical cancer patients is accompanied by considerable acute toxicity. Furthermore, a number of patients were unable to comply with the treatment schedule owing to reasons unrelated to treatment toxicity. Thus, administration of the full chemotherapy dose may be difficult, although the delivery of planned RT was generally not compromised. Additional follow-up is needed to assess the late toxicity of combined modality treatment.     

Role of chemoradiotherapy in intermediate prognosis nasopharyngeal carcinoma

To evaluate the long term impact of concurrent chemoradiotherapy (CCRT) compared to radiotherapy (RT) alone in patients with T2N1M0 nasopharyngeal carcinoma (NPC) retrospectively. Three hundred and ninety-two patients with T2N1M0 NPC according to the AJCC 2002 stage classification system were analyzed. Among them, 211 patients were treated with RT alone and the rest of 181 patients were treated with CCRT. A planned dose of 70 Gy was delivered in 2.0 Gy per fraction over 7 weeks to the primary tumor with 6-MV photons or (60)Cobalt γ-ray. The chemotherapy regimen of cisplatin with a dose of 100mg/m(2) was delivered for 2-3 cycles. With a median follow-up of 66 months (range 2.4-117.1 months), the 5-year overall survival (OS) and disease-free survival (DFS) rates was higher in CCRT group compared to RT alone group, though they failed to reach statistical significance (80.2% vs. 76.6%, P=0.778 and 70.5% vs. 64.2%, P=0.413, respectively). A significant improvement was detected in 5-year relapse-free survival (RFS) rate in CCRT group than RT alone group (91.5% vs. 77.3%, P=0.008). Moreover, chemotherapy was the only independent prognostic factor for the 5-year RFS (P=0.007). Concurrent chemoradiotherapy appeared to improve the 5-year RFS rate for patients with T2N1M0 NPC. Large prospective, randomized clinical studies are needed to confirm its therapeutic gain.     

Adjuvant concurrent chemoradiotherapy with intensity-modulated pelvic radiotherapy after surgery for high-risk, early stage cervical cancer patients

PURPOSE: This study was undertaken to assess local control and toxicity with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy (CCRT) for early stage cervical cancer. PATIENTS AND METHODS: Between June 2004 and February 2007, 54 patients with early stage cervical cancer (stage IB-IIA) with high-risk factors for treatment failure after surgery were treated with adjuvant pelvic IMRT and CCRT. Adjuvant chemotherapy consisted of cisplatin (50 mg/m2) weekly for 4 to 6 courses. All the patients received 50.4 Gy of external beam radiotherapy with IMRT in 28 fractions and 6 Gy of high-dose rate vaginal cuff brachytherapy in 3 insertions. RESULTS: Adjuvant CCRT with IMRT provided good local tumor control in posthysterectomy cervical cancer patients with high-risk pathologic features. The 3-year locoregional control and disease-free survival were 93% and 78%, respectively. Histology and lymph node metastasis were indicators for disease-free survival. Low acute and chronic treatment-related toxicities were noted with IMRT. All the patients completed the radiotherapy treatment without any major toxicity. In terms of chronic toxicity, only 1 patient had grade 3 genitourinary toxicity and none had grade 3 gastrointestinal toxicity. CONCLUSION: Our results indicate that adjuvant CCRT with IMRT technique for adjuvant treatment of early stage cervical cancer is associated with excellent local control and low toxicity.     

Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil,a randomized controlled study

PURPOSE: To determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy (CCRT) vs. 5-fluorouracil (5-FU) CCRT for locally advanced pancreatic cancer. METHODS AND MATERIALS: Thirty-four patients with locally advanced pancreatic cancer were studied. Eighteen patients were randomized to receive GEM CCRT (600 mg/m(2)/wk for 6 weeks) and 16 patients to receive bolus 5-FU CCRT (500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks). All patients were to receive 3D-CRT 50.4-61.2 Gy at 1.8-Gy/d fractions and GEM (1000 mg/m(2) weekly for 3 weeks repeated every 4 weeks) after RT. RESULTS: The median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group (p = 0.027 and p = 0.019, respectively). The quality-adjusted life month survival time was 11.2 +/- 0.5 months for GEM CCRT and 6.0 +/- 0.3 months for 5-FU CCRT patients (p <0.001). The response rate was 50% (four complete responses and five partial responses) for GEM CCRT and 13% (two partial responses) for 5-FU CCRT (p = 0.005). Pain control was 39% for GEM CCRT and 6% for 5-FU CCRT (p = 0.043). Grade 3-4 neutropenia (34% vs. 19%), thrombocytopenia (0% vs. 7%), nausea (33% vs. 31%), vomiting (17% vs. 19%), hospitalization days per month of survival (7.4 +/- 1.7 days vs. 8.0 +/- 1.3 days), and full dose of RT received (78% vs. 75%) were not significantly different between the GEM CCRT and 5-FU CCRT patients. CONCLUSION: GEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability.     

Treatment Interruption During Concurrent Chemoradiotherapy of Uterine Cervical Cancer; Analysis of Factors and Outcomes

Background: To evaluate factors which effect treatment interruption during concurrent chemoradiotherapy(CCRT) and overall survival in patients with uterine cervical cancer stage IB2-IVA in Srinagarind Hospital.Materials and Methods: Between January 2006 and December 2007, 107 patients with stage IB2-IVA as FIGOstaging, 2000, were treated with CCRT in Srinagarind Hospital. Factors which caused treatment interruptionsand impacted on overall survival were reviewed and analyzed. Results: Twenty of 107 patients had treatmentinterruption during CCRT in patients with uterine cervical cancer stage IB2-IVA in Srinagarind Hospital. Thecauses of treatment interruption were as follows: hematologic toxicity was found in 16 of 20 cases, 12 cases withgrade 2 and 4 cases with grade 3; three of 20 cases had gastrointestinal toxicities, 1 case with grade 2 and 2cases with grade 3; one case had grade 3 skin toxicity. The mean total treatment time of the uninterrupted andinterrupted groups were significantly different (78.98 days vs 161.80 days, p <0.001). The patients who couldtolerate≥5 cycles of cisplatin administration had significantly higher mean white blood counts (WBC) (9,769 cells/mm3 vs 7,141 cells/mm3, p=0.02). The mean initial hemoglobin (Hb) in the uninterrupted group was significantlyhigher than the interrupted group (11.5 mg% vs 10.3 mg%, p=0.03). Other factors including age, KPS, initialplatelets, initial serum creatinine levels showed no statistical significance. The 3-year overall survival of theuninterrupted group was better than in the interrupted group (78.6% vs 55.0%, p=0.03). Conclusions: Theinitial Hb and WBC levels were significantly correlated with treatment interruption during CCRT in patientswith uterine cervical cancer. The 3-year overall survival of the uninterrupted group was significantly better thaninterrupted group. These factors may then be used indirectly to predict the outcomes of treatment.     

Feasibility and effectiveness of postoperative adjuvant concurrent chemoradiation therapy in Japanese patients with high-risk early-stage cancer of the uterine cervix

BACKGROUND: This study was undertaken to evaluate the feasibility and effectiveness of postoperative concurrent chemoradiation (CCRT) in patients with high-risk early-stage cervical cancer who were treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: From July 2001 to September 2005, CCRT was performed in 37 patients who had undergone radical hysterectomy with pelvic lymph node dissection at Nagoya University Hospital. Adjuvant chemotherapy consisted of cisplatin (70 mg/m(2) on day 1) and 5-fluorouracil (5-FU; 700 mg/m(2) per day on days 1-4) every 4 weeks for a total of three cycles. Pelvic radiotherapy was started concurrently with the first cycle of chemotherapy. The radiation dose was 45 Gy in 25 fractions. A nonrandomized control group of 52 patients who had undergone radiation therapy alone after radical hysterectomy between 1991 and 2000 served for historical comparison. RESULTS: In the CCRT group, the incidences of grade 3/4 toxicities were 24.3% for neutropenia, 8.1% for nausea and vomiting, and 18.9% for diarrhea. The 5-year progression-free survival (PFS) rates in the CCRT group and control group were 89.2% and 69.2%, respectively (P = 0.0392). CONCLUSION: This study showed that adjuvant CCRT with cisplatin and 5-FU could be safely performed and improved the prognosis in Japanese patients with high-risk early-stage cervical cancer after radical hysterectomy.     

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

PURPOSE: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). METHODS AND MATERIALS: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. RESULTS: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. CONCLUSIONS: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Concurrent weekly docetaxel chemotherapy in combination with radiotherapy for stage III and IVA-B nasopharyngeal carcinoma

Background and Purpose: Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Methods and Materials: Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Results: Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Conclusions: Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.     

同步放化疗对宫颈鳞癌细胞增殖、凋亡及细胞周期的影响

目的:探讨局部晚期宫颈鳞癌细胞对同步放化疗应答的分子机制。方法:49例患者被分为2组:单纯放疗组(RT)和同步放化疗组(CCRT)。在治疗前和治疗中[RT组:放疗10 Gy后;CCRT组:放疗10 Gy+(DDP+5-FU)×1个周期]分别活检留取标本,用FCM、TUNEL及免疫组化检测细胞周期、凋亡以及PCNA的表达。结果:RT组和CCRT组治疗中较治疗前AI及凋亡阳性率均明显升高(P<0.05,P<0.001),治疗中CCRT组凋亡率显著高于RT组(P=0.03);PCNA的表达CCRT组较RT组降低更明显(P=0.005)。治疗中RT组细胞周期大部分被阻滞在G2/M期,而CCRT组大部分被同时阻滞在S和G2/M期。结论:CCRT治疗局部晚期宫颈鳞癌中化疗和放疗有协同作用,其机制可能为通过抑制细胞增殖以及阻滞细胞周期于S和G2/M期,使细胞周期同步化,继而诱导肿瘤细胞的凋亡实现的。     

Long-Term Outcomes and Sites of Failure in Locally Advanced,Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial

Objectives: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. Methods: Patients aged 18–70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). Results: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. Conclusions: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.     

A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study

PURPOSE: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. METHODS AND MATERIALS: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. RESULTS: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. CONCLUSIONS: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered.     

Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results.

PURPOSE: A prospective, randomized, phase III study was performed to evaluate the feasibility and efficacy of concurrent weekly oxaliplatin with radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From January 2001 to January 2003, 115 patients with locoregionally advanced NPC were randomly assigned to either radiotherapy (RT) alone (56 patients) or concurrent chemoradiotherapy (CCRT; 59 patients). All patient characteristics were well balanced in both arms. CCRT with oxaliplatin 70 mg/m2 weekly was administered for six doses from the first day of RT. RESULTS: All patients were eligible for toxicity and response analysis. Compliance with the protocol treatment was excellent, with 97% of patients completing all planned doses of oxaliplatin, and a lack of high-grade toxicity was observed. After a median follow-up time of 24 months, there was a significant difference in overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) in favor of the CCRT arm. The 2-year OS rates were 100% for the CCRT arm and 77% for the RT arm (P = .01). The 2-year MFS rates were 92% for the CCRT arm and 80% for the RT arm (P = .02). The 2-year RFS rates were 96% for the CCRT arm and 83% for the RT arm (P = .02). CONCLUSION: CCRT with weekly oxaliplatin is feasible and improves OS, MFS, and RFS rates in patients with locoregionally advanced NPC. Therefore, further randomized trials including oxaliplatin are warranted.     

不同治疗方式对术后伴中危因素Ⅰ-ⅡA期宫颈癌预后影响

目的 比较不同治疗方式对伴中危因素的Ⅰ-ⅡA期宫颈癌患者的生存差异,探讨早期宫颈癌术后伴中危因素患者的最佳治疗模式。方法 回顾分析2007-2016年间收治的包含中危因素的323例宫颈癌术后患者,比较观察(NT)、单纯化疗(CT)、放疗(RT)及同步放化疗(CCRT)方式对生存的影响。Kaplan-Meier法生存分析,Logrank检验差异,Cox模型行预后因素分析。结果 全组的5年PFS、OS为79.0%、84.8%。单因素及多因素分析肿瘤大小>4 cm、治疗方式是影响PFS的因素(P=0.017、0.002),危险因素个数、治疗方式是影响OS的因素(P=0.042、0.000)。全组中RT及CCRT均可改善患者预后(P=0.007、0.000)。亚组分析中任意1个中危因素(低危组),CT能够延长5年PFS (P=0.026),在改善5年OS上相近(P=0.692);与NT及CT相比,RT及CCRT均能改善患者预后(P=0.006、0.000),但RT与CCRT相近(P=0.820、0.426)。≥2个中危因素(高危组)中,与CT相比,CCRT能提高患者的5年PFS (P=0.006),但不能延长患者5年OS (P=0.107);RT与CCRT比较,CCRT均可改善患者的预后(P=0.028、0.039)。结论 仅有1个中危因素时,RT也能改善预后;伴有≥2个中危因素时,CCRT更能改善患者的预后。     

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation

BackgroundConcomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial.Patients and methodsTotally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m², epirubicin 75 mg/m² and paclitaxel (Taxol) 175 mg/m² (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m² (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients).ResultsSixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT.ConclusionIC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.     

High dose-rate brachytherapy for elderly patients with uterine cervical cancer

BACKGROUND: The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix. METHODS: From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively. RESULTS: The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34). CONCLUSION: Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.     

Anal canal carcinoma: early-stage tumors < or =10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy

PURPOSE: To investigate the clinical history, management, and pattern of recurrence of very early-stage anal canal cancer in a French retrospective survey. METHODS: The study group consisted of 69 patients with Stage Tis and T1 anal canal carcinoma < or =1 cm treated between 1990 and 2000 (12 were in situ, 57 invasive, 66 Stage N0, and 3 Stage N1). The median patient age was 67 years (range, 27-83 years). Of the 69 patients, 66 received radiotherapy (RT) and 3 with in situ disease were treated by local excision alone without RT. Twenty-six patients underwent local excision before RT (12 with negative and 14 with positive surgical margins). Of the 66 patients who underwent RT, 8 underwent brachytherapy alone (median dose, 55 Gy), 38 underwent external beam RT (median dose, 45 Gy) plus a brachytherapy boost (median boost dose, 20 Gy), and 20 underwent external beam RT alone (median dose, 55 Gy). RESULTS: Of the 69 patients, 68 had initial local control. Of the 66 patients treated by RT, 6 developed local recurrence at a median interval of 50 months (range, 13-78 months). Four patients developed local failure outside the initial tumor bed. Of the 3 patients with Tis treated by excision alone, 1 developed local recurrence. No relation was found among prior excision, dose, and local failure. The 5-year overall survival, colostomy-free survival, and disease-free survival rate was 94%, 85%, and 89%, respectively. The rate of late complications (Grade 1-3) was 28% and was 14% for those who received doses <60 Gy and 37% for those who received doses of > or =60 Gy (p = 0.04). CONCLUSION: Most recurrences occurred after a long disease-free interval after treatment and often outside the initial tumor site. These small anal cancers could be treated by RT using a small volume and moderate dose (40-50 Gy for subclinical lesions and 50-60 Gy for T1).     

Operable Stages IB and II cervical carcinomas: a retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy

PURPOSE: To evaluate our data concerning prognostic factors and treatment toxicity in a series of operable cervical carcinomas. METHODS AND MATERIALS: Between May 1972 and January 1994, 414 patients with cervical carcinoma, staged according to the 1995 FIGO staging system (286 Stage IB1, 38 Stage IB2, 56 Stage IIA, and 34 Stage IIB with 1/3 proximal parametrial involvement), underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection (N+: n = 68). Group I included 168 patients who received postoperative radiation therapy (RT): 64 patients had low-dose-rate vaginal brachytherapy with a median total dose (MTD) of 50 Gy; 93 patients had external beam pelvic RT (EBPRT) with an MTD of 45 Gy over 5 weeks, followed by low-dose-rate vaginal brachytherapy (MTD: 20 Gy); and 11 patients had EBPRT alone (MTD: 50 Gy over 6 weeks). Group II included 246 patients treated with preoperative low-dose-rate uterovaginal brachytherapy (MTD: 65 Gy); 32 of these 246 patients also received postoperative EBPRT (MTD: 45 Gy over 5 weeks) delivered to the parametria and pelvic nodes. Mean follow-up from the beginning of treatment was 106 months. RESULTS: First events included isolated locoregional recurrences (35 patients), isolated distant metastases (27 patients), and locoregional recurrences with synchronous metastases (13 patients). The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB. Multivariate analysis showed that independent factors influencing the probability of DFS were as follows: cervical site (exocervical or endocervical vs. both endo- and exocervical, relative risk [RR]: 1.77, p = 0.047), vascular space invasion (no vs. yes, RR: 1.95, p = 0.041), age (>51 years vs. 1 cm: 83% vs. 41%, respectively, p = 0.001). The overall postoperative complication rate was 10% in Group I and 9% in Group II (p = 0.7). The rate of postoperative ureteral complications requiring surgical intervention was lower in Group I than in Group II (0.6% vs. 2.3%, respectively, p = 0.03). The overall 10-year rate for Grade 3 and 4 late radiation complications was 10.4%. Postoperative EBPRT significantly increased the 10-year rate for Grade 3 and 4 late radiation complications (yes vs. no: 22% vs. 7%, respectively, p = 0.0002). CONCLUSION: The prognosis for patients with cervical carcinoma was not influenced by the sequence of adjuvant RT (preoperative uterovaginal brachytherapy vs. postoperative RT) for Stages IB, IIA, and IIB with 1/3 proximal parametrial involvement. However, postoperative EBPRT increased the risk of late radiation complications.