Intensity-modulated radiation therapy for intermediate-risk prostate cancer: does ADT still have an impact in the dose-escalated external beam radiation therapy era?

BACKGROUND: This study aimed to investigate the effect of androgen deprivation therapy (ADT) on the survival of intermediate-risk prostate cancer (IR-PCA) patients treated with dose-escalated external beam radiation therapy (DE-EBRT), and to determine the group that will benefit from ADT. METHODS: We analysed 620 IR-PCA patients treated with DE-EBRT at two institutions. Variables were adjusted using the stabilised inverse probability of treatment weighting method (sIPTW) between radiation therapy (RT) and RT plus ADT groups. Biochemical relapse-free survival (bRFS) rate and overall survival (OS) rate were compared using Kaplan-Meier analysis and log-rank test. Cox proportional hazard analysis (CPH) was conducted to detect unfavorable risk factors. RESULTS: This study included 405 patients; with 217 and 188 patients in the RT and RT plus ADT groups, respectively. The prescribed radiation dose was 78 Gy in 39 fractions. The median follow-up time was 82.0 months. After sIPTW-adjustment, 214.3 and 189.7 patients were assigned to the RT and RT plus ADT groups, respectively. The 7-year bRFS and OS were 89.3% and 94.6% in RT group and 92.3% and 91.0% in RT plus ADT group, respectively. Before and after sIPTW adjustment, no statistically significant differences were found in these endpoints between treatment groups. Multivariate CPH for bRFS revealed Gleason score (GS) 4 + 3 as an unfavorable risk factor, and ADT improved biochemical control of them. CONCLUSION: ADT may not always be effective in all Japanese IR-PCA patients treated with DE-EBRT, but it can improve biochemical control in patients with GS 4 + 3.

Prediction and prevention of central nervous system relapse in patients with extranodal natural killer/T-cell lymphoma.

Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies.

Long-term outcomes and central nervous system relapse in extranodal natural killer/T-cell lymphoma.

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

Outcomes of intensity-modulated radiation therapy for intermediate- or high-risk prostate cancer: a single-institutional study.

BACKGROUND: There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer. METHODS: We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed. RESULTS: The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24-154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2-3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity. CONCLUSIONS: Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.

Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a subtype of mature T- and natural killer cell lymphomas characterized by its association with Epstein-Barr virus and extranodal involvement. Although there is geographic variance in the frequency of ENKL, its clinical features are similar between Western countries and endemic areas, such as East Asia. Anthracycline-containing chemotherapy is not recommended to treat ENKL. No standard treatment has been established based on the results of randomized controlled trials. In patients with localized disease, radiotherapy is a core component of the recommended first-line therapy. Radiotherapy administered at 50 to 54 Gy, extended involved-site radiotherapy considering tumor invasiveness, and the use of intensity modulated radiation therapy or volumetric modulated arc therapy are associated with efficacy of radiotherapy. Although the use of concurrent chemoradiotherapy has been supported by the results of clinical trials, accumulating evidence supports the use of sequential chemoradiotherapy with non-anthracycline-containing regimens that include l-asparaginase and/or platinum anticancer agents. l-asparaginase-containing chemotherapy is a key component of first-line treatments for systemic ENKL. Hematopoietic stem cell transplantation is recommended as a front-line consolidation therapy for newly diagnosed advanced-stage ENKL. Newer agents including immune checkpoint inhibitors are being investigated for treating ENKL. In this modern ENKL treatment era, multidisciplinary efforts are needed to identify the best timing and sequencing of radiotherapy, l-asparaginase, platinum, newer agents, and hematopoietic stem cell transplantation.

Outcomes analysis of pre-brachytherapy MRI in patients with locally advanced cervical cancer.

INTRODUCTION: Various brachytherapy options are available for treating cervical cancer. This study investigated whether pre-brachytherapy magnetic resonance imaging (MRI) findings could help identify the appropriate brachytherapy technique for cervical cancer. METHODS: We retrospectively evaluated patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose rate brachytherapy treatment between December 2009 and September 2015. Patients who could not undergo MRI at pre-treatment and/or pre-brachytherapy and complete radical radiotherapy were excluded. Conventional intracavitary brachytherapy was the preferred treatment for ≤4 cm and symmetrical tumors. Non-conventional intracavitary brachytherapy, including interstitial brachytherapy, was the preferred treatment for bulky tumors, asymmetrical tumors, tumors with severe vaginal invasion, or bulky barrel-shaped tumors. The 3-year rates of overall survival, disease-free survival, and local control were compared using the Kaplan-Meier method and the log-rank test. Overall survival and local control rates were assessed using Cox regression analysis to identify risk factors for poor overall survival and local control outcomes. RESULTS: A total of 146 patients were included in the study. The median tumor sizes were 52 mm (range 17-85) at the pre-treatment MRI and 30 mm (range 0-78) at the pre-brachytherapy MRI. Six patients had International Federation of Gynecology and Obstetrics (FIGO) stage IB2, 67 patients had stage II, 64 patients had stage III, and nine patients had stage IVA disease. A total of 124 (85%) patients had squamous cell carcinoma and 22 (15%) patients had adenosquamous cell carcinoma or adenocarcinoma. The MRI findings showed severe vaginal invasion (pre-treatment: 19 patients, pre-brachytherapy: 10 patients), asymmetrical bulky tumors (pre-treatment: 28 patients, pre-brachytherapy: 16 patients), and severe corpus invasion (pre-treatment: 39 patients, pre-brachytherapy: 18 patients). Based on the pre-brachytherapy MRI findings, non-conventional intracavitary brachytherapy was administered to 34 (23.3%) patients. Brachytherapy seemed to be appropriate for 133 (91.1%) patients and inappropriate for 13 (8.9%) patients. The 3-year rates were 84.2% for overall survival and 90.1% for local control. Grade 3 late rectal complications occurred in two (1%) patients. Multivariate analysis showed that tumor characteristics (size, shape, and extent of invasion) were not risk factors, although inappropriate brachytherapy was significantly related to poor local control (p<0.001). CONCLUSION: Pre-brachytherapy MRI may help to select appropriate brachytherapy for cervical cancer and reduce the likelihood of inappropriate brachytherapy leading to poor local control.

Phase II Trial of Neoadjuvant Chemotherapy, Chemoradiotherapy, and Laparoscopic Surgery with Selective Lateral Node Dissection for Poor-Risk Low Rectal Cancer.

PURPOSE: The aim of this study is to evaluate the safety and efficacy of induction modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab followed by S- 1-based chemoradiotherapy in magnetic resonance imaging (MRI)-defined poor-risk locally advanced low rectal cancer. PATIENTS AND METHODS: This was a prospective phase II trial at a single comprehensive cancer center. The primary endpoint was the pathological complete response (pCR) rate. Eligible patients had clinical stage II-III low rectal adenocarcinoma with any of the following MRI-defined poor-risk features: circumferential resection margin (CRM) ≤ 1 mm, cT4, positive lateral nodes, mesorectal N2 disease, and/or requiring abdominoperineal resection. Patients received six cycles of mFOLFOX6 with 5 mg/kg bevacizumab followed by oral S-1 (80 mg/m2/day on days 1-14 and 22-35) plus radiotherapy (50.4 Gy). Surgery was conducted through a laparoscopic approach. Lateral node dissection was selectively added when the patient had enlarged lateral nodes. RESULTS: A total of 43 patients were enrolled. Grade 3-4 adverse events occurred in nine patients during induction chemotherapy and in five patients during chemoradiotherapy. One patient declined surgery with a clinical complete response. Forty-two patients underwent surgery, and 16 had pCR [37.2%, 95% confidence interval (CI) 24.4-52.1%]. All underwent R0 resection without conversion, including combined resection of adjacent structures (n = 14) and lateral node dissection (n = 30). Clavien-Dindo grade 3-4 complications occurred in six patients (14.3%). With median follow-up of 52 months, six developed recurrences (lung n = 5, local n = 1; 3-year relapse-free survival 86.0%). CONCLUSIONS: This study achieved a high pCR rate with favorable toxicity and postoperative complications in poor-risk locally advanced low rectal cancer. Multicenter study is warranted to evaluate this regimen.

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs.

Epstein-Barr virus-negative extranodal "true" natural killer-cell lymphoma harbouring a KDM6A mutation.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an extranodal aggressive T or NK-cell lymphoma that is characteristically associated with Epstein-Barr virus (EBV) infection and cytotoxic tissue-destructive features. Although ENKTL is described as a distinct entity according to the 2008 WHO classification, a considerable complexity is associated with the differential diagnosis of other T-cell lymphomas with respect to tumour cell origins, locations, and the presence of EBV infection, as well as molecular and cytogenetic abnormalities. Here, we report a rare case of EBV-negative ENKTL, where the absence of EBV in the true NK-lineage cells was confirmed by extensive phenotypic and genotypic analyses. Furthermore, using the next-generation sequencing approach, we identified mutations in the tumour suppressor genes KDM6A and TP53. The clinicopathological characteristics were almost similar to those of EBV-positive ENKTL, except for the absence of EBV and histologically apparent angioinvasiveness. This is the first reported ENKTL case with mutations in the KDM6A gene. KDM6A is one of the histone-modifying genes that are mutated in many human diseases including haematological cancers. Epigenetic regulation of gene expression has recently been demonstrated in ENKTL, and a similar pathway is thought to play an oncogenic role in EBV-negative ENKTL. Our report shows the extent of comprehensive examination required before making a definitive diagnosis for NK- and T-cell neoplasms and broadens the therapeutic options for potential targets.

A Clinical Evaluation of American Brachytherapy Society Consensus Guideline for Bulky Vaginal Mass in Gynecological Cancer.

OBJECTIVES: American Brachytherapy Society (ABS)-recommended interstitial brachytherapy (IBT) should be considered for bulky vaginal tumor thicker than 5 mm. The aim of this study was to evaluate the ABS consensus guideline for patients with severe vaginal invasion based on our long-term follow-up results. METHODS/MATERIALS: The study included 7 patients with vaginal cancer and 14 patients with cervical cancer invading to the lower vagina. Based on prebrachytherapy magnetic resonance imaging findings, patients received intracavitary brachytherapy (ICT) for vaginal tumors 5 mm or less or IBT for vaginal tumors less than 5 mm. Nine patients received ICT and the remaining 12 patients received IBT. For dosimetric comparison, an experimental recalculation as the virtual IBT for patients actually treated by ICT, and vice versa, was performed. RESULTS: The 5-year local control rate for all tumors was 89.4%. No differences in local control between ICT- and IBT-treated groups were observed (P = 0.21). One patient experienced a grade 3 rectal complication. There were no significant differences in the CTV D90 and rectum D2cc between the 2 groups (P = 0.13 and 0.39, respectively). In the dosimetric study of ICT-treated patients, neither the actual ICT plans nor the experimental IBT plans exceeded the limited dose for organs at risk, which were recommended in the guideline published from the ABS. In the IBT-treated patients, D2cc for bladder and rectum of the experimental ICT plans was significantly higher than for the actual IBT plans (P < 0.001 and <0.001, respectively), and 11 experimental ICT plans (92%) exceeded the limited dose for bladder and/or rectum D2cc. CONCLUSIONS: Tumor control and toxicity after selected brachytherapy according to vaginal tumor thickness were satisfactory; IBT instead of ICT is recommended for patients with vaginal tumor thickness greater than 5 mm to maintain bladder and/or rectum D2cc.

[Primary peripheral T-cell lymphoma of the vagina incidentally found at cervical cancer screening].

A 50-year-old woman was referred to our hospital because a mass lesion had been palpable through the vaginal wall during a cervical cancer screening examination. A contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed marked thickening of the vaginal wall, constituting a mass 96 mm in diameter. Abnormal FDG uptake was observed in the vaginal mass, but no other lesions were detected by positron emission tomography (PET/CT). A transvaginal biopsy from the tumor revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Although endoscopic examinations revealed no signs of infiltration in either the bladder or the rectum, the MRI findings suggested invasion into the adjacent rectal wall. She achieved complete remission after six courses of biweekly THP-COP therapy, to which field radiation (39.6 Gy) was added. PTCL of the vagina is rare and this case therefore merits description in the literature.

Low dose palliative radiotherapy for refractory aggressive lymphoma.

AIM: To determine the efficacy of low-dose palliative radiotherapy in patients with refractory aggressive lymphoma. BACKGROUND: There are few reports on the administration of palliative radiotherapy to patients with aggressive lymphoma. MATERIALS AND METHODS: The present study included 11 patients with 30 sites of aggressive lymphoma (diffuse large cell lymphoma, n = 7; mantle cell lymphoma, n = 2; follicular large cell lymphoma, n = 1; and peripheral T cell lymphoma, n = 1). The patients received local palliative radiotherapy after receiving a median of 4 chemotherapy regimens. The radiotherapy doses administered to the 30 sites were as follows: 8 Gy, single fraction (n = 27); 6 Gy, single fraction (n = 1); 4 Gy, single fraction (n = 1); and 4 Gy, 2 fractions (n = 1). RESULTS: The complete response rate was 45% (5/11); the partial response rate was 36% (4/11). Toxicity occurred at one irradiated site (the mandibular), which showed temporal acute gingivitis; however, medication was not required. Retreatment was required for 3 sites on the head (parotid, face and mandible) due to persistent discomfort. None of the other sites (27/30) required retreatment. A patient with refractory DLBCL underwent radiotherapy (4 Gy, single fraction) for hepatic hilar lymph node involvement but did not recover from jaundice and died of DLBCL. CONCLUSIONS: Eight Gray single fraction radiotherapy was one of meaningful options for the treatment of refractory aggressive lymphoma in terms of its efficacy and the incidence of adverse events. The use of 8 Gy single fraction radiotherapy is therefore recommended for achieving local control in patients with refractory aggressive lymphoma.

Four types of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: classification of IBTR based on precise pathological examination.

We classified ipsilateral breast tumor recurrences (IBTRs) based on strict pathological rules. Ninety-six women who were surgically treated for IBTR were included. IBTRs were classified according to their origins and were distinguished based on strict pathological rules: relationship between the IBTR and the primary lumpectomy scar, surgical margin status of the primary cancer, and the presence of in situ lesions of IBTR. The prognosis of these subgroups were compared to that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from the scar. Distant-disease free survival of IBTR that occurred close to the scar with in situ lesions and a negative surgical margin of the primary cancer (NP occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR that occurred close to the scar without in situ lesions (true recurrence (TR) that arose from residual invasive carcinoma foci, TRinv) had significantly poorer prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and a positive surgical margin of the primary cancer (TR arising from a residual in situ lesion, TRis) had more late recurrences than NPcs. Precise pathological examinations indicated four distinct IBTR subtypes with different characteristics.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2014 for treatment of colorectal cancer.

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

[Optimal parameter decision method in VMAT for lung tumors with respiratory motions].

When performing lung cancer treatments using volumetric modulated arc therapy (VMAT) technique, dose error related to respiratory motion of tumors and multi leaf collimator (MLC) movement may occur. The dose error causes daily dose variation in multiple fractionations irradiation. The purpose of this study is to verify the influence of the respiratory motion and the MLC movement on the daily dose variation, and to confirm the feasibility of deciding robust planning parameter against the dose variation. We prepared 5 VMAT plans for imitating lung tumor in thorax dynamic phantom. Dose calculations of these plans were done taking into account the respiratory motions. We examined the relation between dose variation and two parameters that were number of respiration in an arc and MLC gap width. We presented the relationship between the dose variation and each parameters using regression analysis, and we could derive the approximation formula for estimating the dose variation using these parameters. We could estimate dose variation in another VMAT plans using the approximation formula and another plans parameters. By confirming dose variation in planning procedure using this estimation method, we may decide planning parameter taking the dose variation into account. So, we could establish the estimation method to decide adequate planning parameters in VMAT.

Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αß T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.

Successful use of endoscopic argon plasma coagulation for hemorrhagic radiation cystitis: a case report.

Hemorrhagic radiation cystitis is an example of a typical radiotherapy-induced adverse event. However, the optimal treatment for hemorrhagic radiation cystitis is not known. There are limited data regarding the use of argon plasma coagulation for hemorrhagic radiation cystitis. Here, we present the use of argon plasma coagulation using a gastrointestinal endoscope to treat hemorrhagic radiation cystitis. The patient was a 75-year-old male patient with hemorrhagic radiation cystitis due to external beam irradiation for prostate adenocarcinoma. Six years after radiotherapy, the patient presented with macroscopic hematuria over the preceding 4 months, and laboratory investigations revealed a low hemoglobin level. The hematuria was not controlled with 2 days of bladder irrigation using normal saline. Thus, argon plasma coagulation using an upper gastrointestinal endoscope was considered for treatment of the hemorrhagic radiation cystitis. The cystoscopic examination revealed diffuse radiation cystitis with oozing telangiectasia and coagula. All of the bleeding sites and telangiectasia were coagulated using argon plasma coagulation. Following treatment, the patient's clinical symptoms improved and did not recur. The hemoglobin level also recovered. No complications associated with the treatment were observed during the 6-month follow-up period. Thus, argon plasma coagulation using a gastrointestinal endoscope is a safe and effective treatment for hemorrhagic radiation cystitis.

Longitudinal change in health-related quality of life after intensity-modulated radiation monotherapy for clinically localized prostate cancer.

PURPOSE: The purpose of the study is to assess longitudinal changes in general and disease-specific health-related quality-of-life (HRQOL) indices after intensity-modulated radiotherapy (IMRT) monotherapy for patients with localized prostate cancer (PCA). METHODS: Between 2006 and 2010, 91 patients with localized PCA underwent IMRT monotherapy and were enrolled into this prospective study. At baseline, and at 3, 6, 12, and 24 months after IMRT, the general and prostate-specific HRQOL were estimated using physical (PCS) and mental component summaries (MCS) calculated using the Medical Outcomes Study 8-Item Short Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC). RESULTS: For 2 years, there were no significant changes in EPIC scores in all subscales of urinary domain, hormonal function, and bother. Bowel and sexual function scores decreased after IMRT and did not return to those at baseline (p = 0.006 and < 0.001, respectively). PCS began to decrease at 3 months after IMRT and then returned to the baseline score at 24 months. In contrast, the MCS score began to significantly increase after IMRT, and thereafter the score remained constant until 24 months (p < 0.001). On multivariate logistic regression analysis, urinary (p = 0.003) and sexual functions (p = 0.0005) at baseline were identified as significant predictors of EPIC urinary irritative/obstructive score and sexual function at 24 months after IMRT. CONCLUSION: Urinary function, including irritative/obstruction symptoms and hormonal function, was not affected by IMRT. However, bowel and sexual function decreased after IMRT. These findings will provide important information for PCA patients considering IMRT.