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.     

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.     

Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy

This study investigated the prognostic significance of portal vein tumor thrombosis (PVTT) response in hepatocellular carcinoma (HCC) patients treated with localized concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 100 patients treated with CCRT for UICC Stage T2–4N0M0 HCC with PVTT between 2002 and 2011. The radiotherapy (RT) volume included both primary tumor and PVTT, and the median radiation dose was 45 Gy. Treatment response was evaluated for up to 6 months after RT. With respect to PVTT response to treatment, complete response (CR) and partial response (PR) were achieved in 14% and 48% of patients, respectively, yielding an objective response (OR) rate of 62%. PVTT size (≤3cm diameter) was associated with a higher rate of a CR (P = 0.001). The median overall survival (OS) was 11.6 months. Independent prognostic factors for OS were OR of the tumor to RT and a CR of the PVTT. Achieving an OR in both the tumor and the PVTT demonstrated a significant correlation with improved survival (P = 0.002). Progression of intrahepatic metastasis was affected not by CCRT but by the clinical features of the PVTT, particularly the initial PVTT site. PVTT response following CCRT seems prognostically significant. CR of the PVTT was associated with improved survival. Achieving an OR in both the tumor and PVTT was also associated with improved survival.     

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.     

Real-world outcomes of postmastectomy radiotherapy in breast cancer patients with 1–3 positive lymph nodes: a retrospective study

Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1–3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand. Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001–2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients). Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model. Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1–3 node positive early-stage breast cancer.     

The impact of abdominal compression on outcome in patients treated with stereotactic body radiotherapy for primary lung cancer

The aim of this study was to evaluate the impact of abdominal compression (AC) on outcome in patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer. We retrospectively reviewed data for 47 patients with histologically proven non-small cell lung cancer and lung tumour motion ≥8 mm treated with SBRT. Setup error was corrected based on bony structure. The differences in overall survival (OS), local control (LC) and disease-free survival (DFS) were evaluated to compare patients treated with AC (n = 22) and without AC (n = 25). The median follow-up was 42.6 months (range, 1.4–94.6 months). The differences in the 3-year OS, LC and DFS rate between the two groups were not statistically significant (P = 0.909, 0.209 and 0.639, respectively). However, the largest difference was observed in the LC rate, which was 82.5% (95% CI, 54.9–94.0%) for patients treated without AC and 65.4% (95% CI, 40.2–82.0%) for those treated with AC. After stratifying the patients into prognostic groups based on sex and T-stage, the LC difference increased in the group with an unfavourable prognosis. The present study suggests that AC might be associated with a worse LC rate after SBRT using a bony-structure-based set-up.     

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.     

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II–III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II–III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II–III NSCLC in the real-world setting.     

Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice

Niemann-Pick C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of free cholesterol in lysosomes. We have previously reported that oxidative stress is the main upstream stimulus activating the proapoptotic c-Abl/p73 pathway in NPC neurons. We have also observed accumulation of vitamin E in NPC lysosomes, which could lead to a potential decrease of its bioavailability. Our aim was to determine if dietary vitamin E supplementation could improve NPC disease in mice. NPC mice received an alpha-tocopherol (α-TOH) supplemented diet and neurological symptoms, survival, Purkinje cell loss, α-TOH and nitrotyrosine levels, astrogliosis, and the c-Abl/p73 pathway functions were evaluated. In addition, the effect of α-TOH on the c-Abl/p73 pathway was evaluated in an in vitro NPC neuron model. The α-TOH rich diet delayed loss of weight, improved coordination and locomotor function and increased the survival of NPC mice. We found increased Purkinje neurons and α-TOH levels and reduced astrogliosis, nitrotyrosine and phosphorylated p73 in cerebellum. A decrease of c-Abl/p73 activation was also observed in the in vitro NPC neurons treated with α-TOH. In conclusion, our results show that vitamin E can delay neurodegeneration in NPC mice and suggest that its supplementation in the diet could be useful for the treatment of NPC patients.     

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes

Background

The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1–3, 4–9 and ≥10 positive axillary nodes). Methods: A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as ‘Radio + /ECE + ’, ‘Radio–/ECE + ’, ‘Radio + /ECE–’ or ‘Radio–/ECE–’ according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. Results: ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1–3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4–9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). Conclusion: In our study, regardless of the ECE status, PMRT didn''t significantly improve the LRFFS for patients with 1–3 or ≥10 positive axillary nodes. However, for patients with 4–9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.     

Prognostic significance of inflammatory response markers for locally advanced squamous cell carcinoma of the external auditory canal and middle ear

We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4–70.0) Gy, with daily fractions of 1.8–2.0 Gy. The median follow-up period was 25 months (range, 6–137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.     

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.     

Comparison of Preoperative Nutritional Indexes for Outcomes after Primary Esophageal Surgery for Esophageal Squamous Cell Carcinoma

Background: This study aimed to compare the controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) for predicting postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing esophagectomy. Methods: We retrospectively reviewed the data of 1265 consecutive patients who underwent elective esophageal surgery. The patients were classified into no risk, low-risk, moderate-risk, and high-risk groups based on nutritional scores. Results: The moderate-risk (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.24–1.92, p < 0.001 in CONUT; HR: 1.61, 95% CI: 1.22–2.12, p = 0.001 in GNRI; HR: 1.65, 95% CI: 1.20–2.26, p = 0.002 in PNI) and high-risk groups (HR: 1.91, 95% CI: 1.47–2.48, p < 0.001 in CONUT; HR: 2.54, 95% CI: 1.64–3.93, p < 0.001 in GNRI; HR: 2.32, 95% CI: 1.77–3.06, p < 0.001 in PNI) exhibited significantly worse 5-year overall survival (OS) compared with the no-risk group. As the nutritional status worsened, the trend in the OS rates decreased (p for trend in all indexes < 0.05). Conclusions: Malnutrition, evaluated by any of three nutritional indexes, was an independent prognostic factor for postoperative survival.     

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2–135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.     

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.     

Association of Sarcopenia and Expression of Interleukin-16 in Gastric Cancer Survival

We designed the present work to explore the connection between sarcopenia and interleukin-16 (IL-16) expression and their integrated relation with gastric cancer (GC) survival. We deemed the sex-specific third lumbar vertebra skeletal muscle index cutoffs for sarcopenia to be ≤40.8 and ≤34.9 cm²/m² in male and female patients, respectively. Immunohistochemistry was carried out to detect IL-16 levels among GC tissues of the patients. We determined overall survival (OS) and relapse-free survival (RFS) by univariate and multivariate analyses. This study included 225 GC cases, with an average age of 62.7 years. There were 41 (18.2%) female patients, and 107 (47.5%) patients had sarcopenia. Sarcopenia and high IL-16 expression were identified as independent factors to predict OS (hazard ratios [HR] = 1.64 and 1.79, 95% confidence interval [CI] = 1.25–2.23 and 1.16–2.78, respectively) and RFS (HR = 1.43 and 1.60, 95% CI = 1.15–2.95 and 1.10–2.37, respectively). There were more cases showing high IL-16 expression detected in the sarcopenia group (55.7% vs. 37.3%, p = 0.003). Later, we grouped the patients with sarcopenia and IL-16 expression and discovered that the patients with sarcopenia and IL-16 upregulation displayed the poorest OS (HR = 3.02; 95% CI = 1.64–5.91) and RFS (HR = 2.34; 95% CI = 1.47–4.69). In conclusion, more IL-16 upregulation was noted in GC patients with sarcopenia. Sarcopenia accompanied by high IL-16 expression remarkably indicates a dismal prognosis in GC patients. This suggests that these biomarkers may be able to identify patients with GC with poor prognosis and enhance prognostication.     

Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma

Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated.A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child–Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy.The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II–III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed.PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation.     

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.     

Modified Glasgow Prognostic Score is predictive of prognosis for non-small cell lung cancer patients treated with stereotactic body radiation therapy: a retrospective study

We aimed to assess the predictive value of the modified Glasgow prognostic score (mGPS) in patients with non-small cell lung cancer (NSCLC) who underwent stereotactic body radiation therapy (SBRT). We retrospectively reviewed the records of 207 patients, with a median age of 79 years. The pretreatment mGPS was calculated and categorized as high (mGPS = 1–2) or low (mGPS = 0). The median follow-up duration was 40.7 months. The five-year overall survival (OS), progression-free survival (PFS) and time to progression (TTP) rates were 44.3%, 36% and 54.4%, respectively. Multivariate analysis revealed that mGPS was independently predictive of OS (hazard ratio [HR] 1.67; 95% confidence interval 1.14–2.44: P = 0.009), PFS (HR 1.58; 1.10–2.28: P = 0.014) and TTP (HR 1.66; 1.03–2.68: P = 0.039). Patients who had high mGPS showed significantly worse OS (33.3 vs 64.5 months, P = 0.003) and worse PFS (23.8 vs 39 months, P = 0.008) than those who had low mGPS. The data showed a trend that patients with high mGPS suffered earlier progression compared to those with low mGPS (54.3 vs 88.1 months, P = 0.149). We confirmed that mGPS is independently predictive of prognosis in NSCLC patients treated with SBRT.