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Purpose: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma., Results: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages., Conclusions: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age., Patients and Methods: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

Background: To investigate the use of radiotherapy (RT) in China in patients with breast cancer over a 10-year period. A hospital-based, nationwide, multicenter, retrospective epidemiologic study of women with primary breast cancer was conducted., Patients and Methods: Patients were selected randomly in 7 hospitals from 1999 to 2008. Data on overall RT, postmastectomy RT (PMRT), RT after conservative breast surgery (PBRT) and palliative RT (PRT) were recorded. RT use was analyzed, and differences were compared by using the Cochran-Armitage trend test and the χ(2) test. A total of 3732 patients were included: 1009 (27%) received RT, including 688 (18.4%) PMRT, 170 (4.6%) PBRT, 86 (2.3%) PRT, 47 (1.3%) both PMRT and PRT, and 18 (0.5%) other RT., Results: Overall use of RT increased significantly from 1999 to 2008 (2P < .001). There was a slight but significant increase in PMRT (2P = .012) and a 10-fold increase in PBRT (2P < .001); use of PRT was relatively constant (2P = .777). There was a significant difference among regions in the use of RT, PMRT, PBRT, and PRT (2P < .01). Of patients with stage III disease, 51.6% and of those with node-positive stage II disease treated by radical mastectomy, 21% had received PMRT. In patients treated by using breast conservative surgery, 83.7% received PBRT, which was not affected by stage., Conclusion: In summary, in China, the overall use of RT in patients with breast cancer was quite low, but there was an increasing trend in those treated between 1999 and 2008., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer., Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m(2) (n = 6) once a week for 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m(2)/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity., Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m(2) (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m(2). At 80 mg/m(2), DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea)., Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m(2) twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m(2), comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p =.160), 30.8% (p =.017), and 31.3% (p =.039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma. BALT lymphoma has a favorable prognosis but a persistent progression and relapse risk. Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Although there is now a consensus on asparaginase-based chemotherapy regimens in the treatment of advanced-stage extranodal natural killer/T-cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. Methods: Newly diagnosed stage Ⅲ/Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. Results: The study included 83 newly diagnosed stage Ⅲ/Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase-based regimens compared to non-asparaginase-based regimens significantly prolonged PFS (p = 0.007; HR = 0.48, p = 0.020) and showed a tendency to improve OS (p = 0.064; HR = 0.74, p = 0.359). Gemcitabine-based regimens also exhibited a trend toward improved PFS (p = 0.048; HR = 0.59, p = 0.164) and OS (p = 0.008; HR = 0.67, p = 0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (p = 0.020; HR = 0.40, p = 0.022) and slightly better OS (p = 0.054; HR = 0.79, p = 0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (p = 0.051) and OS (p = 0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. Conclusion: Asparaginase and gemcitabine alone brought a favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration, and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

The study investigated the treatment and prognosis of advanced‐stage extranodal natural killer/T‐cell lymphoma (ENKTL). With a median follow‐up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1‐, 2‐, 3‐ and 5‐year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P =.007), and hematopoietic stem cell transplantation (HSCT) compared to non‐HSCT (P <.001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P =.141). Nine patients ever treated with chidamide achieved a median progression‐free survival (mPFS) and mOS of 53.63 (range, 3.47‐92.33) and 54.80 (range, 5.50‐95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27‐92.33) and 60.65 (range, 53.70‐95.70) months, possibly providing an alternative option for non‐HSCT patients. Non‐anthracycline (ANT)‐ compared to ANT‐, asparaginase (Aspa)‐ compared to non‐Aspa‐ and gemcitabine (Gem)‐ compared to non‐Gem‐based regimens, prolonged PFS (P =.031; P =.005; P =.009) and OS (P =.010; P =.086; P =.003), respectively. Multivariate analysis demonstrated that Gem‐based regimens improved PFS (HR = 0.691, P =.061) and OS (HR = 0.624, P =.037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First‐line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long‐term survival for advanced‐stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT. [ABSTRACT FROM AUTHOR]

Purpose: To determine oncologic outcomes for patients with T4b sinonasal squamous cell carcinoma (SNSCC) treated with either surgery plus radiotherapy or definitive radiotherapy. Materials and Methods: Between January 1999 and December 2016, 85 patients with T4b SNSCC were analyzed retrospectively, there were 54 who received surgery plus radiotherapy (S + RT group) ± chemotherapy and 31 with definitive radiotherapy (RT group) ± chemotherapy. A 1: 2 propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan–Meier method and Cox proportional hazard model were used to determine risk factors on survival outcomes. Results: The median follow‐up time was 76.7 months. The cumulative rates of locoregional control (LRC), distant metastasis‐free survival (DMFS), cancer‐specific survival (CSS), and overall survival (OS) at 5 years for entire cohort were 44.6%, 33.1%, 38.8%, and 33.9% respectively. After PSM, a total of 50 patients in S + RT group and 25 patients in RT group were analyzed. The 5‐year LRC, DMFS, CSS, and OS between S + RT and RT group were 58.6% versus 27.5% (p = 0.035), 42.8% versus 20.0% (p = 0.006), 50.3% versus 22.0% (p = 0.005), 44.5% veruss 20.0% (p = 0.004). The 5‐year survival rates with orbital retention between groups were 32.7% and 15.0%, p = 0.080. Multivariate Cox analysis revealed non‐surgical therapy (HR = 3.678, 95%CI 1.951–6.933) and invasion of cranial nerves (other than maxillary division of trigeminal nerves) (HR = 2.596, 95%CI 1.217–5.535) were associated with decreased OS. Conclusion: The inclusion of surgery in the multimodal management of T4b SNSCC might confer a survival benefit. Further prospective studies comparing the oncologic outcomes of S + RT with RT are warranted. Level of Evidence: 3 Laryngoscope, 133:2222–2231, 2023 [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic value of gross tumor volume (GTV) in early-stage extranodal NK/T-cell lymphoma (ENKTCL) treated with intensity-modulated radiation therapy (IMRT) and explore the interactive effect of GTV and radiotherapy (RT) dose on locoregional recurrence (LRR). Methods: The data of 319 early-stage ENKTCL patients who underwent IMRT were reviewed retrospectively. Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were estimated using Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards regression was performed to identify independent risk factors for survival outcomes. Penalized spline regression was used to flexibly model the association of continuous predictors (GTV and RT dose) with mortality, progression, and relapse. Results: The 5-year OS, PFS, and LRC for the entire cohort were 72.9, 64.4, and 89.9%, respectively. The risks of disease mortality, progression, and recurrence increased steadily with increasing GTV. Patients with GTV < 35 mL had significantly higher 5-year OS (83.0% vs. 59.4%; P < 0.001), PFS (76.7% vs. 48.4%; P < 0.001), and lower 5-year cumulative LRR rate (4.9% vs. 14.5%; P = 0.004), than patients with GTV ≥ 35 mL. The risk of LRR was low with RT doses of 50-56 Gy, independent of GTV. For patients with GTV ≥ 35 mL, dose ≥ 56 Gy was not associated with decreased LRR. Conclusion: Larger GTV is associated with worse survival and higher LRR in early-stage ENKTCL patients treated with IMRT. A dose of 50–56 Gy may be appropriate to achieve lower risk of LRR, regardless of GTV. [ABSTRACT FROM AUTHOR]

Purpose: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis. Methods and materials: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments. Results: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group. Conclusion: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned. [ABSTRACT FROM AUTHOR]

To clarify the effect of postmastectomy radiotherapy (PMRT) on pT 1-2 N 1 breast cancer patients with different molecular subtypes. We retrospectively analyzed the data of 5442 patients with pT 1-2 N 1 breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR). With a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p < 0.001). PMRT was independently associated with reduced LRR after adjustments for confounders (p < 0.001). After grouping the patients according to the molecular subtype of cancer and conducting PSM, we found that the 5-year LRR rates among patients treated with and without PMRT (in that order) were as follows: luminal HER2-negative cancer, 1.9% and 6.5% (p < 0.001); luminal HER2-positive cancer, 3.8% and 13.7% (p = 0.041); HER2-overexpressing cancer, 10.2% and 15.5% (p = 0.236); and triple-negative cancer, 4.6% and 15.9% (p = 0.002). Among patients with HER2-overexpressing and triple-negative cancers, the LRR hazard rate displayed a dominant early peak, and was extremely low after 5 years. However, patients with luminal cancer continued to have a long-lasting high annual LRR hazard rate during follow-up. PMRT significantly reduced the LRR risk in patients with pT 1-2 N 1 luminal and triple-negative breast cancers, but had no effect on the LRR risk in patients with HER2-overexpressing cancer. Patients with different molecular subtypes displayed different annual LRR patterns, and the late recurrence of the luminal subtype suggests the necessity of long-term follow-up to evaluate the efficacy of PMRT. • PMRT reduces LRR of pT 1-2 N 1 luminal and triple-negative breast cancers. • PMRT has no effect on the LRR of HER2-overexpressing breast cancer. • Different molecular subtypes display different annual LRR patterns. • Late LRR beyond 5 years is observed in luminal breast cancers. [ABSTRACT FROM AUTHOR]

Background: Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques.Methods: POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1-3 vs. 4-9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed.Discussion: This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy.Trial Registration: ClinicalTrails.gov , NCT04320979 . Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979. [ABSTRACT FROM AUTHOR]

The phase 3 NCT00793962 trial demonstrated that postmastectomy hypofractionated radiation therapy (HFRT) was noninferior to conventional fractionated radiation therapy (CFRT) in patients with high-risk breast cancer. This study assessed the cost-effectiveness of postmastectomy HFRT vs CFRT based on the NCT00793962 trial. A Markov model was adopted to synthesize the medical costs and health benefits of patients with high-risk breast cancer based on data from the NCT00793962 trial. Main outcomes were discounted lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). We employed a time-dependent horizon from Chinese, French and USA payer perspectives. Model robustness was evaluated with one-way and probabilistic sensitivity analyses. Patients receiving CFRT versus HFRT gained an incremental 0.0163 QALYs, 0.0118 QALYs and 0.0028 QALYs; meanwhile an incremental cost of $2351.92, $4978.34 and $8812.70 from Chinese, French and USA payer perspectives, respectively. Thus CFRT versus HFRT yielded an ICER of $144,281.47, $420,636.10 and $3,187,955.76 per QALY from Chinese, French and USA payer perspectives, respectively. HFRT could maintain a trend of >50% probabilities of cost-effectiveness below a willingness-to-pay (WTP) of $178,882.00 in China, while HFRT was dominant relative to CFRT, regardless of the WTP values in France and the USA. Sensitivity analyses indicated that the ICERs were most sensitive to the parameters of overall survival after radiotherapy. Postmastectomy HFRT could be used as a cost-effective substitute for CFRT in patients with high-risk breast cancer and should be considered in appropriately selected patients. • HFRT is a cost-effective substitute for CFRT for women with high-risk breast cancer. • The incremental cost-effectiveness ratio varied in a time-dependent manner and increased with the time horizon. • Overall survival were the most influential parameter on the incremental cost-effectiveness ratio. [ABSTRACT FROM AUTHOR]

In the multidisciplinary management of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL), with curative intent, radiation therapy is the most efficacious modality and is an essential component of a combined-modality regimen. In the past decade, utilization of upfront radiation therapy and non-anthracycline-based chemotherapy has improved treatment and prognosis. This guideline mainly addresses the heterogeneity of clinical features, principles of risk-adapted therapy, and the role and appropriate design of radiation therapy. Radiation therapy methods (including target volume definition, dose and delivery methods) are crucial for optimizing cure for patients with early-stage ENKTCL. The application of the principles of involved site radiation therapy in this lymphoma entity often leads to a more extended clinical target volume (CTV) than in other lymphoma types because it usually presents with primary tumor invasion, multifocal lesions, or extensive submucosal infiltration beyond the macroscopic disease. The CTV varies across different primary sites and is classified mainly into nasal, nonnasal upper aerodigestive tract (UADT), and extra-UADT entities. This review is a consensus of the International Lymphoma Radiation Oncology Group regarding the approach to radiation therapy, target-volume definition, optimal dose, and dose constraints in ENKTCL treatment. [ABSTRACT FROM AUTHOR]

Purpose: Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods: Conditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated. Results: A total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%. Conclusions: Survival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted. [ABSTRACT FROM AUTHOR]

Background and Purpose: Optimal radiation target volumes for breast cancer patients with their first isolated chest wall recurrence (ICWR) after mastectomy are controversial. We aimed to analyze the regional failure patterns and to investigate the role of prophylactic regional nodal irradiation (RNI) for ICWR. Materials and Methods: Altogether 205 patients with ICWR after mastectomy were retrospectively analyzed. Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent regional recurrence (sRR) and locoregional recurrence (sLRR) rates, and the differences were compared with Gray test. Results: The 5-year sRR rate was 25.2% with median follow-up of 88.6 months. Of the 52 patients with sRR, 30 (57.7%) recurred in the axilla, 29 (55.8%) in supraclavicular fossa (SC), and five (9.6%) in internal mammary nodes. Surgery plus radiotherapy was independently associated with better sLRR and PFS rates (p<0.001). The ICWR interval of ≤ 4 years was associated with unfavorable sRR (p=0.062), sLRR (p=0.014), PFS (p=0.001), and OS (p=0.005). Among the 157 patients who received radiotherapy after ICWR, chest wall plus RNI significantly improved PFS (p=0.004) and OS (p=0.021) compared with chest wall irradiation alone. In the 166 patients whose ICWR interval was ≤ 4 years, chest wall plus RNI provided the best PFS (p<0.001) and OS (p=0.022) compared with chest wall irradiation alone or no radiotherapy. Conclusion: Patients with ICWR have a high-risk of sRR in SC and axilla. Chest wall plus RNI is recommended. [ABSTRACT FROM AUTHOR]

Background and Purpose: We investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC. Materials and Methods: This was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan–Meier method and compared by the log-rank test. Results: Patients were classified into three groups: HER2-negative (HER2−; n = 547), HER2-positve with trastuzumab (HER2+ + T; n = 136), and HER2-positive without trastuzumab (HER2+ − T; n = 110). The HER2+ + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The HER2− group had significantly lower LRR (6.8% vs. 13.9%), DM (22.4% vs. 33.8%) and higher DFS (76.1% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The difference in LRR, DM and DFS at 5 years was not significant between the HER2+ + T group and HER2− group (P >.05). Different annual LRR patterns was found among groups according to HR status. Conclusion: Trastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer. Patients and Methods: We retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat. Results: The median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes. Conclusion: For women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes. [ABSTRACT FROM AUTHOR]

Background: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT.Methods: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model.Results: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728).Conclusions: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of adjuvant radiotherapy after narrow-margin (<1.0 cm) resection in patients with intrahepatic cholangiocarcinoma (ICC) adherent to major vessels.Patients and methods: This retrospective study included 70 ICC patients. Forty-nine patients received narrow-margin (<1.0 cm) hepatectomy and 21 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Twenty-six of 49 were treated with postoperative radiotherapy (Group A), while the remaining 23 did not receive radiotherapy (Group B). Clinical outcomes were compared in the 3 groups. Toxicities of radiotherapy were evaluated.Results: With a median follow-up time of 42 months, the 3-year overall survival (OS) and disease-free survival rates were 55% and 44% for Group A, 20% and 10% for Group B, and 65% and 33% for Group C, respectively. The OS and disease-free survival in Groups A and C were comparable and improved compared to Group B (Group A vs B, P=0.011 and P=0.031; and Group C vs B, P=0.031 and P=0.105). Multivariate analysis showed that receiving narrow-margin resection only (adjusted hazard ratio: 3.73; 95% CI: 1.36–10.25; P=0.001) was a significant poor prognostic risk factor of OS. Group B experienced more intrahepatic recurrence and extrahepatic recurrence than Groups A and C. For Groups A and B, the 3-year intrahepatic recurrence rates were 36% vs 67% (P=0.133) and extrahepatic recurrence rates were 43% vs 65% (P=0.007). Only 2 patients in Group A suffered from grade 3 toxicities. No patient developed classic or nonclassic radiation-induced liver disease.Conclusion: Postoperative radiotherapy following narrow-margin hepatectomy seems to be efficacious and well-tolerated in patients with ICC adjacent to major vessels. [ABSTRACT FROM AUTHOR]

Background & Aims: To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. Methods: This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. Results: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. Conclusions: Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels. [ABSTRACT FROM AUTHOR]

The prognosis and optimal therapy for high-risk early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well defined. This study was conducted to evaluate the prognostic factors and treatment outcomes in patients with stage II NKTCL of the upper aerodigestive tract (UADT-NKTCL). One hundred and twenty-four patients with stage II UADT-NKTCL were enrolled. Primary tumors were located in the nasal cavity ( n = 53) or extranasal UADT ( n = 71). Eighty-four patients were treated with combined modality therapy (CMT), and 40 patients were treated with radiotherapy alone ( n = 30) or chemotherapy alone ( n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all stage II patients were 60.1% and 47.8%, respectively. Primary location and disease extent were the important prognostic factors in univariate and multivariate analyses. CMT significantly improved survival. The 5-year OS and PFS rates were 71.2% and 56.7% for CMT, compared with 35.1% ( p < 0.001) and 26.7% for single modality therapy ( p < 0.001). Survival differences between CMT and single modality therapy were also observed in nasal and extranasal subgroups of UADT-NKTCL. This retrospective study showed significant improvements in OS and PFS in patients who received both chemotherapy and radiotherapy for stage II NKTCL. The findings need further validation in other datasets. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the prognostic importance of rituximab and radiotherapy in patients with primary mediastinal large B-cell lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine patients with PMBCL received CHOP chemotherapy with ( n = 39) or without rituximab ( n = 40), and 60 patients received additional radiotherapy. Patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) had significantly superior survival rates. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 83.7% and 76.7% for R-CHOP, compared with 48.3% ( p = 0.011) and 44.2% ( p = 0.012) for CHOP, respectively. Similarly, the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R-CHOP, and 52.0% ( p = 0.002) and 46.6% ( p = 0.003) with CHOP, respectively. Patients treated with chemotherapy and radiotherapy had better survival and local control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and radiotherapy, and 50.8% ( p = 0.076), 36.9% ( p = 0.008) and 56.4% ( p < 0.001) for chemotherapy alone, respectively. Early stage patients treated with R-CHOP and radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP plus consolidation radiotherapy was associated with excellent survival and LC rates. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze outcomes in adult patients with early stage systemic anaplastic large-cell lymphoma (ALCL) treated with doxorubicin-based chemotherapy and radiotherapy. Forty-six adult patients with early stage systemic ALCL received chemotherapy followed by radiotherapy. All patients except two received chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. Twenty patients had stage I disease, and 26 patients had stage II disease. The 5-yr overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 84.4%, 63.6%, and 90.8%, respectively. The 5-yr OS and PFS rates were 95.0% and 77.4% for Ann Arbor stage I disease, and 75.1% and 51.7% for stage II disease, respectively. Lymph node involvement was the main pattern of disease progression or relapse for these patients. Adult patients with early stage systemic ALCL treated with doxorubicin-based chemotherapy and radiotherapy had a favorable prognosis. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study aimed to evaluate the outcome of patients who had received postmastectomy chest wall radiotherapy using a single electron beam, and to identify the relevant factors that influenced prognosis. Methods: The medical records of patients with breast cancer treated with postmastectomy radiotherapy from January 2000 to December 2004 were retrospectively analyzed (n = 328). Two hundred seventy-one (82.6%) patients were staged as (tumor-nodes-metastasis [TNM]) T3-4, any N, M0; or T1-2, N2-3, M0, and 57 (17.4%) patients were staged as T1-2, N1, M0. All patients received chest wall radiation with a 6-10 MeV electron beam. In addition, 327 patients (99.7%) received supraclavicular node radiation, 67 (20.4%) axillary radiation, and 35 (10.7%) internal mammary chain (IMC) radiation. Chemotherapy with anthracycline and taxane was given to 323 patients (98.5%). Of patients with positive hormone receptor, 183 (82.8%) received hormone therapy and 8 patients with negative and 3 patients with unknown hormone receptor received hormone therapy. Locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences assessed by log-rank test. Results: The median follow-up time was 78 months (range, 5-123 months) for patients who remained alive. The 5-year LRR, DM, disease-free survival and OS rates were 5.9%, 26.2%, 72.5%, and 83.1%, respectively. LRR occurred in 1 or more sites in 21 patients. The 5-year recurrence rates in the chest wall, supraclavicular node, axilla, and internal mammary chain were 1.9%, 2.3%, 2.9%, and 0%, respectively. In multivariate analysis, hormone therapy was the only independent favorable prognostic factor for LRR (P = .017). LRR was significantly associated with DM and OS. The 5-year DM rate was 82.9% and 22.7% (P < .0001) and the 5-year OS rate was 52.8% and 84.7% (P < .0001) for patients with or without LRR. The treatment-related toxicity was low, with the incidence of symptomatic pneumonitis being 0.3%. Conclusions: Breast cancer patients can be treated with postmastectomy single electron beam radiotherapy with excellent local control and low toxicity. [Copyright &y& Elsevier]

Purpose: The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. Methods and Materials: Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose–volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survival were calculated using the Kaplan-Meier method. Results: The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. Conclusions: High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T-cell lymphoma treated with primary radiotherapy. METHODS: Two-hundred fourteen patients were included. There were 182 cases of stage I and 32 cases of stage II disease. Patients received radiotherapy alone (n = 96) or radiotherapy and chemotherapy (n = 118). The median dose was 50 grays, and most patients received doxorubicin-based chemotherapy. RESULTS: The 5-year overall survival (OS) and progression-free survival rates for all patients were 72% and 65%, respectively. Sixty-three patients experienced treatment failure. The 5-year cumulative incidences of locoregional, systemic, and overall failures were 12.0%, 25.5%, and 32.9%, respectively. Stage and paranasal extension were significant predictors for systemic failure. The 5-year cumulative incidence of systemic failure was 22.6% for stage I disease versus 42.7% for stage II disease ( P < .001), and 16.9% for limited disease versus 30.4% for paranasal extension ( P < .001), respectively. Adding chemotherapy to extended involved-field radiotherapy did not significantly decrease the systemic failure rate nor improve survival. The cumulative incidence of systemic failure and OS rate at 5 years were 24.1% and 74.4% for combined modality therapy compared with 28.5% ( P = 0.758) and 69.8% ( P = 0.529) for radiotherapy alone. A very low incidence of cervical lymph node or central nervous system relapse was observed. CONCLUSIONS: Patients with early stage nasal NK/T-cell lymphoma have excellent locoregional control and favorable prognosis with radiotherapy, but patients with stage II disease or paranasal extension are at high risk of systemic failure, emphasizing the importance of integration of optimal radiotherapy with innovative systemic therapy. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether the phenotypic characteristics of the two subtypes of CD56++ and CD56−− lymphoma have relevance for their clinical behavior and prognosis. The immunophenotypes of all patients were confirmed using standard criteria for CD20, CD3ℇε, CD56, cytotoxic molecules (T-cell intracellular antigen-1 [[TIA-1]] and granzyme B), and Ki-67, and in situ hybridization for Epstein--Barr virus (EBV)-encoded RNA (EBER). CD56 was expressed in 90 of 118 (76.3%%) patients. The majority (83.3%%) of patients with nasal natural killer/T-cell lymphoma (NKTCL) presented with CD56++ lymphoma, whereas patients with NKTCL of the extranasal upper aerodigestive tract were more likely to have CD56−− lymphoma (53.6%%, p < 0.000). A lower percentage of expression of granzyme B and Ki-67 (>50%%) was found in patients with CD56−− lymphoma compared with those with CD56++ lymphoma ( p < 0.05). The clinical characteristics and prognosis were comparable between patients with CD56++ and CD56−− lymphomas. The corresponding overall survival and progression-free survival rates were 74.1%% and 56.7%%, respectively, for patients with CD56++ lymphoma compared with 81.6%% and 60.5%% for those with CD56−− lymphoma ( p > 0.05). There was no clinical or prognostic significance in determining the two subtypes of CD56++ and CD56−− NKTCL based on their immunophenotypic profiles, which has clinical implications for pathological diagnosis and insight into disease behavior. [ABSTRACT FROM AUTHOR]

Our objective was to assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiation therapy (RT) in patients with breast cancer. Eligible patients with breast cancer who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times after RT. RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. Five hundred patients were analyzed. All patients underwent chest wall/breast with or without regional nodal irradiation. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, P <.001). The peak incidence of RHT occurred around 6 to 12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid mean dose (Dmean) were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between thyroid Dmean and the risk of RHT. Dmean >21 Gy was the threshold value for predicting RHT (hazard ratio, 2.2; P <.001). The incidence of RHT was high in patients with breast cancer. Thyroid function test should be started no later than 6 months after RT. We recommend that the Dmean of the thyroid should be kept lower than 21 Gy for hypofractionated RT. [ABSTRACT FROM AUTHOR]

To investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer. Post hoc analyses of 584 patients with stage II and III breast cancer from a randomised controlled clinical trial were performed. All patients underwent mastectomy followed by sequential chemotherapy and RT. The optimal cut-off values for the surgery-RT interval (SRI) and the chemotherapy-RT interval (CRI) for overall survival (OS) were determined using the hazard ratio for continuous predictors. The locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and OS rates were estimated using the Kaplan–Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Median follow-up time was 83.5 months. Median SRI and CRI were 168 and 27 days, respectively. An SRI of >210 days was independently associated with higher DM (HR 2.65, 95% CI: 1.49–4.71; HR 2.78, 95% CI 1.51–5.26), lower OS (HR 2.44, 95% CI: 1.28–4.54; HR 2.50, 95% CI: 1.41–4.35), and lower DFS (HR 2.57, 95% CI: 1.45–4.57; HR 2.70, 95% CI: 1.45–5.00) than SRI of <180 or 180–210 days. Furthermore, a CRI of more than 42 days was independently associated with higher DM (HR 1.89, 95% CI: 1.17–3.06; HR 1.96, 95% CI: 1.19–3.22), lower OS (HR 2.44, 95% CI: 1.41–4.35; HR 1.92, 95% CI: 1.10–3.33), and lower DFS (HR 1.84, 95% CI: 1.14–2.96; HR 1.82, 95% CI: 1.12–2.94) than a CRI of <28 or 28–42 days. However, SRI and CRI had no significant effect on LRR. Based on the present findings, the timing of the initiation of RT both after mastectomy and after the completion of adjuvant chemotherapy is crucial for patients with high-risk breast cancer. • Delays in initiating PMRT compromise distant control and survival. • Up to 210 days after mastectomy and 42 days after chemotherapy may be acceptable. • Studies on RT should evaluate endpoints beyond locoregional recurrence. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL).Methods: This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index: >60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status >1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints.Results: Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P > .05).Conclusions: The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL. [ABSTRACT FROM AUTHOR]

• This is a post hoc analysis of 628 patients from a phase III, randomized trial with long-term follow-up of 110.8 months. • Radiation-induced lymphopenia in breast cancer patients after BCS tends to be mild. • The lower pre-RT PLC predicted poorer survival. • Neither nadir PLC during RT nor the recovery of PLC after RT was independently associated with survival. To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to evaluate the effect of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy in patients with node-positive stage II to III (cT1-4N1-2M0) breast cancer.Methods and Materials: A total of 1813 patients from 12 institutions were retrospectively reviewed. Patients were classified into 1 of 3 groups based on the pathologic lymph node status after neoadjuvant chemotherapy: ypN0, ypN1, and ypN2-3. The role of PMRT was separately evaluated in each group. Locoregional control, disease-free survival, and overall survival (OS) were estimated using the Kaplan-Meier method. The effect of PMRT was assessed by propensity score-matched analyses and multivariate Cox analyses.Results: With a median follow-up of 72.9 months, 5-year locoregional control, disease-free survival, and OS rates were 86.3%, 68.4%, and 83.1% for the entire cohort, respectively. There were 490 (27.0%), 567 (31.3%), and 756 (41.7%) patients in the ypN0, ypN1, and ypN2-3 groups, respectively. PMRT significantly improved 5-year OS in the ypN2-3 group (74.2% vs 55.9%; P < .001) but had no effect on 5-year OS in the ypN0 group (93.1% vs 95.5%; P = .517) and ypN1 group (88.4% vs 87.8%; P = .549).Conclusions: With modern systemic therapy, PMRT significantly improved OS in the ypN2-3 group but not in the ypN0 and ypN1 groups. Whether PMRT can be safely omitted in the ypN0 and ypN1 groups should be addressed prospectively. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer.Methods and Materials: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test.Results: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 ± 0.57 × 109/L vs 1.56 ± 0.52 × 109/L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 ± 0.37 × 109/L vs 0.97 ± 0.31× 109/L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 ± 0.28 vs 0.67 ± 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio ≥0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24).Conclusions: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and toxicity profile of sequential intensity modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, and cisplatin (GDP) on previously untreated high-risk, early stage upper aerodigestive tract natural killer/T-cell lymphoma (UADT-NKTCL).Methods and Materials: A phase 2 study was designed, and 40 high-risk patients with stage I(E)/II(E) UADT-NKTCL were enrolled between June 2010 and June 2014. High-risk patients were defined as those with at least 1 predefined risk factor: age >60 years, elevated serum lactate dehydrogenase, regional lymph node involvement, B symptoms, and primary tumor invasion. Patients received extended involved-site IMRT and GDP chemotherapy. The primary endpoint was the 2-year progression-free survival rate. Secondary endpoints were the 2-year overall survival rate, overall response rate, and toxicity.Results: Median follow-up time was 60.1 months. The overall response rate and complete remission rate were 97.5% and 95.0%, respectively. The 2- and 5-year progression-free survival rates were 84.7% and 79.4%, and the corresponding overall survival rates were 89.9% and 82.1%, respectively. The most frequent radiation-induced toxicities were mild mucositis and skin reaction. Grade 3/4 neutropenia (12 of 40 patients), thrombocytopenia (7 of 40), and anemia (2 of 40) were observed during chemotherapy.Conclusions: First-line IMRT followed by GDP represents an effective and well-tolerated protocol for high-risk, early stage UADT-NKTCL. [ABSTRACT FROM AUTHOR]

• Patients with synchronous ipsilateral supraclavicular LNM showed excellent supraclavicular nodal control after multimodality therapy. • Distant metastasis was the major failure pattern. • Supraclavicular lymph node dissection plus RT did not improve outcomes compared with RT alone. • Patients can be classified into three risk groups with different prognosis. To evaluate and compare the outcomes of supraclavicular lymph node dissection plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis. In all, 293 patients with synchronous ipsilateral supraclavicular lymph node metastasis across three centers were included. Of these, 85 (29.0%) received supraclavicular lymph node dissection plus RT (Surgery + RT) and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan–Meier method and multivariate Cox models. Multiple imputation was used for missing data. The median follow-up duration of the RT and Surgery + RT groups were 53.7 and 63.5 months, respectively. For the RT and Surgery + RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing Surgery + RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. Surgery + RT did not improve outcomes of any risk group compared with RT alone. Patients with synchronous ipsilateral supraclavicular lymph node metastasis may not benefit from supraclavicular lymph node dissection. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma (NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns.Methods and Materials: A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy.Results: The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surrounding the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS.Conclusions: Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients. [ABSTRACT FROM AUTHOR]

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL).Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (Dmean) to the parotid glands on xerostomia.Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The Dmean to the parotid glands had a linear correlation with late grade ≥2 xerostomia.Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL. [ABSTRACT FROM AUTHOR]

Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT. [ABSTRACT FROM AUTHOR]