Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V_{15 Gy}) < 120 cc and V_{45 Gy} ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V_{15 Gy} was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.     

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.     

Long-term outcomes of patients with unresectable benign meningioma treated with proton beam therapy

This study aimed to evaluate the long-term efficacy of proton beam therapy (PBT) for unresectable benign meningiomas at the University of Tsukuba, Japan. From 1986–1998, 10 patients were treated at the Particle Radiation Medical Science Center (PRMSC) with a relative biological effectiveness (RBE) value of 1.0 using an accelerator built for physics experiments. The total dose was compensated with an X-ray in three patients. Following that, from 2002–2017, 17 patients were treated with a RBE value of 1.1 at the Proton Medical Research Center (PMRC) which was built for medical use. At the PRMSC, the total dose ranged from 50.4–66 Gy (median: 54 Gy). During the follow-up, which lasted between 3.8 and 31.6 years (median: 25.1 years), the 5-, 10-, 15-, 20- and 30-year local control rates were 100%, and the 5-, 10-, 15-, 20- and 30-year survival rates were 90, 80, 70, 70 and 36%, respectively. One patient died of brainstem radiation necrosis 5.1 years after PBT. At PMRC, the total dose ranged from 45.0–61.2 GyE, with a median of 50.4 GyE. During the follow-up, which lasted between 3 and 17 years with a median of 10.5 years, the 5-, 10- and 15-year local control rates were 94.1%, and the 5-, 10- and 15-year survival rates were 100, 100 and 88.9%, respectively. Neither malignant transformation nor secondary malignancy was observed, indicating that fractionated PBT may be effective and safely control benign unresectable meningioma even for the lifelong period of time.     

Alternating chemoradiotherapy in patients with nasopharyngeal cancer: prognostic factors and proposal for individualization of therapy

The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990–2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4–80.2 Gy) and 66 Gy (range, 40.4–82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis ≥ Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of ≥ Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.     

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.     

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.     

Lactobacillus Kefiri LKF01 (Kefibios®) for Prevention of Diarrhoea in Cancer Patients Treated with Chemotherapy: A Prospective Study

Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3–4) in treated patients is in the range of 10–20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios^®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios^® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3–4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios^®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Stereotactic body radiotherapy for kidney cancer: a 10-year experience from a single institute

The purpose of this retrospective study was to investigate survival outcomes and irradiated tumor control (local control [LC]) and locoregional control (LRC) after stereotactic body radiotherapy (SBRT) for T1 or recurrent T1 (rT1) kidney cancer. Twenty-nine nonconsecutive patients with 30 tumors were included. SBRT doses of 70 Gy, 60 Gy or 50 Gy in 10 fractions were prescribed with a linear accelerator using daily image guidance. The Kaplan–Meier method was used to estimate time-to-event outcomes, and the log-rank test was used to compare survival curves between groups divided by each possible factor. The median follow-up periods for all patients and survivors were 57 months and 69.6 months, respectively. The five-year LC rate, LRC rate, progression-free survival (PFS) rate, disease-specific survival (DSS) rate and overall survival (OS) rate were 94%, 88%, 50%, 96% and 68%, respectively. No significant factor was related to OS and PFS. Three of 24 non-hemodialysis (HD) patients had new-onset-HD because of the progression of underlying kidney disease. Grade 3 or higher toxicities from SBRT did not occur. In conclusion, SBRT for kidney cancer provided a high rate of LC, LRC and DSS with minimal toxicities, but patient selection and indication for SBRT should be done carefully considering the relatively low OS rate.     

Local radiotherapy for pleural dissemination of thymic tumors after initial treatment

Pleural dissemination is a common pattern of failure after initial treatment of thymoma and thymic carcinoma, but there is no standardized treatment. As these tumors are relatively radiosensitive, we investigated the effectiveness of radiotherapy. Twenty patients underwent 33 series of local radiotherapy for 96 pleural dissemination lesions after initial treatment. Conventional radiotherapy (CRT), tomotherapy, and combination of the two were employed in 19, 13, and 1 series, respectively. The median follow-up period after the first irradiation for pleural dissemination was 46 months (range, 14–161). For all 20 patients, overall survival (OS) rates from initial radiotherapy for pleural dissemination were 100% at three years and 86% at five years. Progression-free survival (PFS) rates after 33 series of radiotherapy were 30% at three years and 16% at five years. Local control (LC) rates for 96 lesions were 98% at three years and 96% at five years. In-field recurrence was observed in only two among the 96 lesions. One patient (5%) developed grade 3 radiation pneumonitis and another (5%) developed grade 3 pericardial effusion. No other serious adverse events were observed. When disseminated nodules can be covered within localized fields, local radiotherapy may be a treatment option. Using tomotherapy, multiple lesions can be treated safely.     

Cotrimoxazole prophylaxis and antiretroviral therapy: an observational cohort study in China

Objective

To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV).

Methods

We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200 cells/µL were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses.

Findings

The analysis involved 23 816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6 months of ART was 5.3 and 7.0 per 100 person–years, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.56–0.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6 months (HR: 0.65; 95% CI: 0.59–0.73), 12 months (HR: 0.58; 95% CI: 0.49–0.70), 18 months (HR: 0.49; 95% CI: 0.38–0.63) and 24 months (HR: 0.66; 95% CI: 0.48–0.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50 cells/µL (HR: 0.60; 95% CI: 0.54–0.67), 50–99 cells/µL (HR: 0.66; 95% CI: 0.56–0.78) and 100–199 cells/µL (HR: 0.78; 95% CI: 0.62–0.98).

Conclusion

Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries.     

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0–1 RP (RP_G≤1) group and the Grade 2–5 RP (RP_G≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RP_G≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RP_G≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RP_G≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.     

A retrospective study of small-pelvis radiotherapy plus image-guided brachytherapy in stage I–II non-bulky cervical squamous cell carcinoma

We herein report a retrospective analysis of the efficacy of a combination therapy of pelvic irradiation that excluded the common iliac lymph nodes region and image-guided brachytherapy (IGBT) for non-bulky (≤4 cm) cervical cancer. Thirty-three patients with stage I–II cervical squamous cell carcinoma (≤4 cm) and without pelvic/para-aortic lymphadenopathy who were treated with definitive radiotherapy alone between February 2009 and September 2016 were included. The radiotherapy consisted of CT-based small-pelvis irradiation (whole pelvis minus common iliac lymph node area) of 20 Gy/10 fractions followed by pelvic irradiation with a midline block of 30 Gy/15 fractions and IGBT of 24 Gy/4 fractions (6 Gy/fraction for high-risk [HR] clinical target volume [CTV] D90%). In-room computed tomography (CT) imaging with applicator insertion was used for brachytherapy planning, with physical examinations and diagnostic magnetic resonance imaging (MRI) also being referred to for determination of HR CTV. Over a median follow-up of 60.5 months (range, 7–89), two patients developed distant recurrence and one developed local and distant recurrence. Two patients died from cervical cancer, one from hepatocellular carcinoma and one from non-cancerous disease. The 2/5-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 100%/96.7%, 93.8%/90.6% and 93.9%/93.9%, respectively. No pelvic/para-aortic lymph node recurrence was observed. There were no late complications of grade 3 or higher in the small bowel, large bowel/rectum, or bladder. Our results suggest that a combination therapy of IGBT plus small-pelvis irradiation excluding common iliac lymph nodes provides reasonable clinical outcomes and can be a treatment option in non-bulky (≤4 cm) cervical squamous cell carcinoma.     

Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39–85) years. The median follow-up term was 16.3 (range, 2–53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.     

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0–11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right–left, superior–inferior, and anterior–posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2–3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.     

Prognostic factors associated with radiotherapy for cervical cancer with computed tomography-detected para-aortic lymph node metastasis

Patients with cervical cancer diagnosed with a para-aortic lymph node (PALN) metastasis by computed tomography (CT) scan were analyzed to identify associated prognostic factors. A total of 55 patients were reviewed, and 27 of these patients underwent extended-field radiotherapy (EFRT). The median PALN dose in patients receiving EFRT was 45 Gy (range, 27–57.6 Gy). Of the 55 patients, 28 underwent pelvic radiotherapy (RT); concurrent chemoradiotherapy (CCRT) was administered to 41 patients. The Kaplan–Meier method was used to calculate the actuarial rate. Multivariate analysis was performed using the Cox proportional hazards model. Five-year overall survival (OS) rates were 41% and 17.9% in patients undergoing EFRT and pelvic RT (P = 0.030), respectively. Age < 53 years (P = 0.023), FIGO Stage I–II (P = 0.002), and treatment with EFRT (P = 0.003) were independent predictors of better OS. The use of CCRT (P = 0.014), Stage I–II (P = 0.002), and treatment using EFRT (P = 0.036) were independent predictors of distant metastasis. In patients undergoing EFRT plus CCRT, the 5-year OS was 50%. Three-year PALN disease-free rates were 8.8%, 57.9% and 100% (P < 0.001) in CCRT patients who received PALN doses of 0 Gy, ≤45 Gy and ≥50.4 Gy, respectively. Although PALN metastasis is thought to be distant metastasis in cervical cancer, EFRT plus CCRT shows a good outcome, particularly in younger patients in an early FIGO stage. Cervical cancer with a PALN metastasis should not be considered incurable. Doses ≥50.4 Gy for treating PALN may result in better disease control.     

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.     

Long-term results of definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma

PurposeThe present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events.ResultsThe median age was 66 years (range, 41–83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients.ConclusionWe showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed.     

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.