Concurrent chemoradiotherapy for T3–4 and N0–1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3–4 and N0–1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3–4 N0–1 M0, World Health Organization Type 2–3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m²). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3–4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis–free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.     

Phase I study of oral S-1 and concurrent radiotherapy in patients with head and neck cancer

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m² b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64–70 Gy in 32–35 fractions over 6–7 weeks. A total of 12 patients (3 patients at 40 mg/m², 6 patients at 60 mg/m², and 3 patients at 80 mg/m²) were enrolled in this trial. At the dose of 80 mg/m², two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m². Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m².     

Analysis of simultaneous modulated accelerated radiotherapy (SMART) for nasopharyngeal carcinomas

The purpose of this study was to analyze the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) in patients with nasopharyngeal carcinoma (NPC). A total of 97 patients who underwent SMART for NPC between August 2005 and November 2011 were evaluated. The prescribed dose was 69.9 Gy/30 fractions at 2.33 Gy/fraction to the primary gross tumor volume (PGTV) including the nasopharynx gross target volume and the positive neck lymph nodes, and 60 Gy/30 fraction at 2.0 Gy/fraction to the PCTV1; 54 Gy/30 fractions at 1.8 Gy/fraction was given to the PCTV2. Among 59 patients with local advanced disease, 31 patients received concurrent chemoradiotherapy (chemo-RT) with a regimen consisting of 135 mg/m² paclitaxel on Day 1 and 25 mg/m² cisplatin on Days 1–3. The median follow-up period was 42 months. The local control rate (LCR), distant metastases-free survival (DMFS) and overall survival (OS) rates were 93.3%, 90.3% and 91.6% at 3 years, and 87.6%, 87.9% and 85.7% at 5 years, respectively. There was no significant difference in outcome with respect to these three indicators for Stage III and IV disease treated with/without concurrent chemoradiotherapy (P > 0.05). Acute toxicities included Grade 3 mucositis, skin desquamation, and leucopenia, which occurred in 78 (80.4%), 8 (8.2%), and 45 (46.4%) patients, respectively. No patient had a Grade 3–4 late toxicity. SMART was associated with a favorable outcome for NPC with acceptable toxicity. The local-regional control was excellent but distant metastasis remains the main risk. The combination of SMART and chemotherapy needs to be optimized through further studies to enhance outcomes for locally advanced diseases.     

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.     

Neoadjuvant capecitabine,bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study

The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m² twice daily at Dose Level 1, with a planned escalation to 900 mg/m² twice daily at Dose Level 2. Within 6.1–10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m² twice daily.     

多西他赛同步三维适形放疗治疗老年晚期非小细胞肺癌效果观察

目的观察多西他赛同步三维适形放疗治疗老年晚期非小细胞肺癌(NSCLC)的疗效及不良反应。方法对病理学或细胞学证实的32例NSCLC患者,给予多西他赛35 mg/m2,静脉滴注,于放疗前1 d开始,每周1次,共4次。施行立体适形放疗(3D-CRT),3~4 Gy/次,5次/周,总量40~50 Gy。结果初治患者RR86.4%,复治患者RR40%,ORR68.8%,中位生存期10个月。不良反应:食道炎40.6%,白细胞减少46.9%,放射性肺炎18.8%,无治疗相关性死亡。结论多西他赛同步三维适形放疗治疗老年晚期NSCLC疗效满意,耐受性好。     

Efficacy and safety of nedaplatin-based concurrent chemoradiotherapy for FIGO Stage IB2–IVA cervical cancer and its clinical prognostic factors

Cisplatin-based concurrent chemoradiotherapy (CCRT) is a standard treatment for cervical cancer, but nedaplatin-based CCRT is not routinely administered. We evaluated the efficacy and safety of nedaplatin-based CCRT (35 mg/m² weekly) and analyzed prognostic factors for survival among 52 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB2–IVA cervical cancer treated from 1999 to 2009. Patients were treated with a combination of external beam radiotherapy of 40–56 Gy (in 20–28 fractions) and 13.6–28.8 Gy (in 2–4 fractions) of high-dose-rate (HDR) intracavitary brachytherapy or 18 Gy (in 3 fractions) of HDR interstitial brachytherapy. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis. Acute and late toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 52 months. The median patient age was 63 years. The 5-year OS, PFS and LC rates were 78%, 57% and 73%, respectively. Multivariate analysis showed that histologic type, maximum tumor diameter, and pretreatment hemoglobin level were independent risk factors for PFS. Regarding adverse effects, 24 patients (46%) had acute Grade 3–4 leukopenia and 5 (10%) had late Grade 3 gastrointestinal toxicities. No patient experienced renal toxicity. Nedaplatin-based CCRT for FIGO Stage IB2–IVA cervical cancer was efficacious and safe, with no renal toxicity. Histologic type, maximum tumor diameter, and pretreatment hemoglobin level were statistically significant prognostic factors for PFS.     

放疗联合多西紫杉醇、顺铂同期及辅助化疗治疗局部晚期鼻咽癌的临床观察

目的观察多西紫杉醇联合顺铂同期放化及辅助化疗治疗局部晚期鼻咽癌的疗效及安全性。方法 2008年1月～2009年12月共48例局部晚期鼻咽癌患者进入研究,放疗总剂量70～76Gy/35～38次,同期于第1、22、43天给予3周期多西紫杉醇+DDP的同期化疗,放疗结束2周后,再给予3周期多西紫杉醇+DDP的辅助化疗。结果中位随访25个月,66.7%的患者完成了全部6周期的化疗,75.0%的患者完成3个周期的同期化疗,70.8%的患者完成了3个周期的辅助化疗。2年局部控制率、总生存率和无进展生存率分别为89.6%、90.1%和77.8%。主要不良反应为中性粒细胞减少、粘膜炎和体重下降,但经过积极支持治疗,大多可完成治疗。结论初步结果表明对于局部晚期鼻咽癌患者,该方案依从性高,早期疗效较好,不良反应可耐受。     

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent ¹⁹²Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.     

Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy

The purpose of this study was to assess the efficacy and toxicity of definitive radiotherapy (RT) for the recurrence of epithelial ovarian cancer, which is limited to one or two gross regions, after complete remission had been achieved with aggressive front-line therapy. Twenty-seven patients were treated with definitive RT and were retrospectively analyzed. Their median tumor size was 3.0 cm. Twenty-six (96%) patients received external irradiation at a median total dose of 60 Gy, and a median daily dose of 2 Gy. Only two patients received intracavitary brachytherapy. Twenty (74%) of the 27 patients received systemic chemotherapy for the treatment of a limited recurrent tumor followed by definitive RT. Six (22%) of the patients received concurrent chemotherapy and seven (26%) of the patients also underwent regional hyperthermia during definitive RT. Twenty-two (82%) patients had an objective response (CR: 11, PR: 11). The 2-year overall survival, progression-free survival and local (in-field) control rates after RT were 53%, 39% and 96%, respectively. The toxicities were mild, no Grade 3 or higher toxicity was observed in any of the patients. The tumor size( < 3 cm), period between front-line therapy and RT (≥2 year) and objective tumor response (CR) were significant prognostic factors of the overall survival rate. In conclusion, definitive RT for limited recurrence of epithelial ovarian cancer achieves a better local control rate without severe toxicity, and it may therefore be a potentially effective modality for inducing long-term survival in selected patients.     

Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer

To evaluate the efficacy of incomplete treatment protocols of cisplatin in concurrent chemoradiation for locally advanced cervical carcinoma. This retrospective study was performed in 165 consecutively treated patients with locally advanced cervical cancer who received a weekly cisplatin regimen. The number of weekly cisplatin cycles of each patient was recorded and used to discriminate between patients. Local control, disease free survival, distant metastasis-free survival, and toxicities were calculated using the software package SPSS version 15.0. Ninety-two patients (55%) completed the planned protocol of six cycles of weekly cisplatin. With the median follow-up time of 38.2 months, the 3-year local control rate differed significantly in the two patient groups (95.4% of 6 cycles versus 84.8% of < 6 cycles; p = 0.028). No statistical significance was observed for disease-free survival (74.6% versus 74.5%; p = 0.22) and distant metastasis-free survival (76.5% vs. 75.7%; p = 0.88). In conclusion, the plan completion of concurrent cisplatin with radiotherapy was responsible for better local control. However, differences in disease-free survival and distant metastasis-free survival were not statistical significant.     

A modified Phase I trial of radiation dose escalation in 3D conformal radiation therapy with concurrent vinorelbine and carboplatin chemotherapy for non-small-cell lung cancer

The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy for patients with non-small cell lung cancer (NSCLC); however, it was unclear whether this dose could be safely administered to Asian patients due to differences in their physique compared to Western patients. We therefore conducted a modified Phase I trial to determine whether 70 Gy could be safely delivered to Chinese patients with NSCLC undergoing 3D-conformal radiation therapy (3D-CRT) with concurrent chemotherapy. Previously untreated NSCLC patients received 3D-CRT (2 Gy/day, 5 fractions per week). Three dose levels were examined: 62, 66 and 70 Gy. Two cycles of concurrent chemotherapy (vinorelbine and carboplatin) were started on the first day of radiation therapy. Dose-limiting toxicity (DLT) was defined as severe or life-threatening side effects that altered the continued implementation of chemoradiotherapy. Among the 19 patients recruited in this study, most of the haematologic and non-haematologic toxicities were mild to moderate and clinically manageable. Only one patient, in the 70 Gy cohort, experienced a DLT of Grade 3 radiation-induced pneumonia. The overall response rate was 77.8% (14/18). The median progression-free survival (PFS) was 12 months, and the 1-year PFS was 37.6%. Our results support both the feasibility of incorporating 3D-CRT with concurrent vinorelbine and carboplatin and a dose escalation to 70 Gy for Chinese patients with NSCLC, based on the acceptable toxicity and encouraging overall response and survival rates. A further evaluation of this regimen in a prospective Phase II trial is ongoing.     

Radiotherapy for Stage I or II hypopharyngeal carcinoma

Hypopharyngeal squamous cell carcinoma (HPSCC) is usually diagnosed at an advanced stage, and early-stage HPSCC is relatively rare. Because of the rarity of early-stage HPSCC, few reports have been published on the efficacy of radiotherapy (RT) in its treatment. We retrospectively reviewed the clinical records of 45 consecutive patients with Stage I and II HPSCC from May 1991 to June 2010. Patient characteristics were as follows: median age, 66 years (range, 44–90 years); male/female, 39/6; and T1/T2, 27/18. The irradiation dose ranged from 60 to 72 Gy (median: 70 Gy). Of the 45 patients, 21 underwent concurrent chemotherapy. With a median follow-up period of 62 months, the 5-year overall survival rate was 81%. Local failure occurred in 5 patients, and the 5-year local control rate was 83%. All local recurrences were successfully salvaged by surgery. The 5-year functional larynx preservation rate was 92%. Acute toxicity was manageable. Grade 3 laryngeal edema and Grade 3 hypothyroidism occurred in 1 patient each. No other late adverse events of Grade 3 or greater were observed. Based on these results, RT seemed to be an effective treatment modality for early HPSCC, with favorable organ preservation and acceptable adverse events. Early detection and accurate management of local recurrence and second malignancy was deemed to be critical.     

局部晚期非小细胞肺癌同步与序贯放化疗的近期疗效观察

目的 评价同步放化疗与序贯放化疗治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效.方法 对39例局部NSCLC患者进行回顾性分析,其中序贯放化疗23例、同步放化疗28例.采用常规分割照射,总量60～65 Gy.序贯治疗采用化疗2个周期后再放疗;同步治疗采用每周给药.结果 同步放化疗的近期有效率(62.5%)高于序贯放化疗(43.5%),两种治疗方法的临床症状缓解率近似.结论 同步放化疗可提高局部晚期NSCLC的近期疗效,提倡采用多西紫杉醇+三维适形放疗的同步治疗方法.     

Efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for locally advanced rectal cancer

Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2–3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m²/day, was orally administered during radiotherapy. A total dose of 45–50.4 Gy was delivered in 25–28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6–10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients.     

Clinical trial of carbon ion radiotherapy for gynecological melanoma

Carbon ion radiotherapy (C-ion RT) is an advanced modality for treating malignant melanoma. After we treated our first case of gynecological melanoma using C-ion RT in November 2004, we decided to conduct a clinical trial to evaluate its usefulness for the treatment of gynecological melanoma. The eligibility criteria for enrollment in this study were histologically proven malignant melanoma of the gynecological regions with lymph node metastasis remaining in the inguinal and pelvic regions. The small pelvic space, including the GTV and the metastatic lymph node, was irradiated with up to a total dose of 36 GyE followed by a GTV boost of up to a total dose of 57.6 GyE or 64 GyE in 16 fractions. A series of 23 patients were treated between November 2004 and October 2012. Patient age ranged from 51–80 with a median of 71. Of the tumor sites, 14 were located in the vagina, 6 in the vulva, and 3 in the cervix uteri. Of the 23 patients, 22 were irradiated with up to a total dose of 57.6 GyE, and 1 patient was irradiated with up to a total dose of 64 GyE. Chemotherapy and interferon-β were also used to treat 11 of the patients. Acute and late toxicities of Grade 3 or higher were observed in 1 patient treated with concurrent interferon-β. The median follow-up time was 17 months (range, 6–53 months). There was recurrence in 14 patients, and the 3-year local control and overall survival rates were 49.9% and 53.0%, respectively. C-ion RT may become a non-invasive treatment option for gynecological melanoma.     

NP方案联合同步放疗治疗晚期非小细胞肺癌临床分析

目的评价国产长春瑞滨（盖诺）联合顺铂同步放化疗治疗晚期非小细胞肺癌的疗效及毒副反应。方法将96例Ⅲ期NSCLC患者随机分为两组,化放组在放疗时及放疗后进行4周期化疗,化疗用药盖诺25mg／m^2,在每个周期的第1、8天静脉滴注,顺铂25mg／m^2第1～3天静脉滴注;单放组行单纯放疗。结果化放组有效率72．5％,单放组有效率为44．4％,化放组的有效率明显高于单放组（P=0．008）。化放组和单放组的1、2年生存率分别为70．6％、29．4％和51．1％、20％,中位生存时间分别为18个月和13个月,两组比较差异有统计学意义（P=0．0407）。结论NP方案联合同步放疗是治疗晚期非小细胞肺癌的安全有效的治疗方法,值得进一步临床研究。     

Impact of concurrent chemotherapy on definitive radiotherapy for women with FIGO IIIb cervical cancer

The purpose of this retrospective study is to investigate the impact of concurrent chemotherapy on definitive radiotherapy for the International Federation of Gynecology and Obstetrics (FIGO) IIIb cervical cancer. Between 2000 and 2009, 131 women with FIGO IIIb cervical cancer were treated by definitive radiotherapy (i.e. whole pelvic external beam radiotherapy for 40–60 Gy in 20–30 fractions with or without center shielding and concomitant high-dose rate intracavitary brachytherapy with 192-iridium remote after loading system for 6 Gy to point A of the Manchester method). The concurrent chemotherapy regimen was cisplatin (40 mg/m²/week). After a median follow-up period of 44.0 months (range 4.2–114.9 months) and 62.1 months for live patients, the five-year overall survival (OS), loco-regional control (LRC) and distant metastasis-free survival (DMFS) rates were 52.4, 80.1 and 59.9%, respectively. Univariate and multivariate analyses revealed that lack of concurrent chemotherapy was the most significant factor leading to poor prognosis for OS (HR = 2.53; 95% CI 1.44–4.47; P = 0.001) and DMFS (HR = 2.53; 95% CI 1.39–4.61; P = 0.002), but not for LRC (HR = 1.57; 95% CI 0.64–3.88; P = 0.322). The cumulative incidence rates of late rectal complications after definitive radiotherapy were not significantly different with or without concurrent chemotherapy (any grade at five years 23.9 vs 21.7%; P = 0.669). In conclusion, concurrent chemotherapy is valuable in definitive radiotherapy for Japanese women with FIGO IIIb cervical cancer.     

High-dose concurrent chemo–proton therapy for Stage III NSCLC: preliminary results of a Phase II study

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.     

Multimodal approaches including three-dimensional conformal re-irradiation for recurrent or persistent esophageal cancer: preliminary results

The purpose of this study was to assess the toxicity and efficacy of multimodal approaches, including three-dimensional conformal re-irradiation, for patients with recurrent or persistent esophageal cancer after radiotherapy. Thirty-one patients with esophageal cancer treated with three-dimensional conformal re-irradiation were retrospectively analyzed. Of the 31 patients, 27 patients received concurrent chemotherapy, and 14 patients underwent regional hyperthermia during the re-irradiation. We divided the patients into two groups on the basis of their clinical condition: the curative group (n = 11) or the palliative group (n = 20). Severe toxicities were detected in one patient with Grade 3 esophageal perforation in the curative group, and 5 patients had a Grade 3 or higher toxicity of the esophagus in the palliative group. Advanced T stage at the time of re-irradiation was found to be significantly correlated with Grade 3 or higher toxicity in the esophagus. For the curative group, 10 (91%) of 11 patients had an objective response. For the palliative group, symptom relief was recognized in 8 (57%) of 14 patients with obvious swallowing difficulty. In conclusion, in the curative group with early-stage recurrent or persistent esophageal cancer, the multimodal approaches, including three-dimensional conformal re-irradiation, may be feasible, showing acceptable toxicity and a potential value of promising results, although further evaluations especially for the toxicities of the organs at risk are required. In the palliative group, the benefit of our therapy may be restrictive because severe esophageal toxicities were not uncommon in the patients with advanced T stage at the time of re-irradiation.