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Background: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). Methods: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training (N = 9,259) and two validation cohorts (N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. Results: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival (p < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA < 2,000 (EBVlow); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBVhigh) and T1-2N2/T2-3N1 EBVlow; AHR3, T1-2N2/T2-3N1 EBVhigh and T3N2/T4N0 EBVlow; AHR4, T3N2/T4 N0-1 EBVhigh and T1-3N3/T4N1-3 EBVlow; AHR5, T1-3N3/T4 N2-3 EBVhigh. Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98–12.67), hazard discrimination (5.29 versus 6.69–13.35), explained variation (0.248 versus 0.164–0.225), balance (0.385 versus 0.438–0.749) and C-index (0.707 versus 0.662–0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts (p < 0.001 for both). Conclusion: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. Implications for Practice: The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology. Cancer patients have an increased risk of contracting COVID‐19. This article addresses the challenges associated with managing cancer patients during the COVID‐19 infection pandemic and suggests some practical approaches. [ABSTRACT FROM AUTHOR]

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules. What's new?: Given limited recent advances in chemotherapeutic regimens, there is an urgent need to develop targeted therapies for metastatic nasopharyngeal carcinoma (NPC) that reduce toxicity and improve survival benefit. This review of clinical trials with monoclonal antibodies against checkpoint inhibitors shows that anti‐PD1 is a potential treatment option for patients with recurrent/metastatic NPC. Camrelizumab combination therapy achieved the best clinical outcome, but was associated with a high rate of serious adverse events. As immunotherapy gets incorporated into standard treatments, issues of optimal combinations with targeting agents and immune adjuvants and sequence with chemotherapy and radiation therapy will need to be addressed. [ABSTRACT FROM AUTHOR]

In this study, whole exome sequencing was conducted on tumor samples and paired germline samples from patients with Sertoli‐Leydig cell tumors to explore not only DICER1 mutations for Chinese populations but also other genetic variations related to pathogenesis and prognosis, which could lay a preliminary foundation for genetic counseling. [ABSTRACT FROM AUTHOR]

This letter to the editor remarks on additional considerations for the management of febrile neutropenia during the COVID‐19 pandemic, in response to the letter by Boutayeb et al. [ABSTRACT FROM AUTHOR]

Compelling evidence has solidified the notion of early treatment intensification in managing patients with metastatic hormone‐sensitive prostate cancer (mHSPC). Landmark trials have provided Level 1 evidence for the survival benefits achieved by combining multiple agents. The efficacy of combined therapy relies not only on how treatment is intensified but also on how it is de‐escalated. This underscores the importance of tailored treatment approaches, potentially involving a reduction in therapy for specific patients, to strike a balance between the benefits of hormonal treatment and its associated adverse effects. While de‐escalation of therapy in mHSPC remains challenging due to limited evidence, it is recommended for elderly or frail patients, those with poor performance status, or experiencing significant toxicity. However, for patients with excellent prostate‐specific antigen responses or favourable biomarkers, decisions should be personalised, weighing the potential benefits of continued treatment against the risk of long‐term side effects, using risk stratification tools where appropriate. [ABSTRACT FROM AUTHOR]

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC. [ABSTRACT FROM AUTHOR]

Purpose To describe and compare outcomes in men with initially presumed indolent prostate cancer receiving definitive radiation therapy after active surveillance (AS) versus those in a risk-matched cohort undergoing up-front radiation therapy. Methods and Materials Men prospectively enrolled in an AS program between 1992 and 2014 and subsequently undergoing curative radiation therapy (ie, image guided radiation therapy [IGRT] or low-dose-rate brachytherapy [LDR-BT]) were identified. Biochemical relapse–free rate (bRFR), metastasis-free rate (mFR), and overall survival (OS) were compared against a cohort of men treated up front, matched by age, clinical prognostic indices (risk group, prostate-specific antigen, cT category, Gleason score, percentage of involved biopsy cores), and radiation therapy modality. Results Of 1070 patients in the AS registry, 200 underwent definitive radiation therapy (143 IGRT and 57 LDR-BT) after a median of 32.9 (interquartile range [IQR] 20.6-59.8) months on surveillance. Main reasons for treatment were grade and volume upgrading (57.5% and 26%, respectively). Median follow-up after radiation therapy was 4.9 (IQR 3.1-7.5) years. At 5 years the bRFR, mFR, and OS were, respectively, 97%, 99%, and 98.5%. No patient died of prostate cancer. Adequate risk-matching was confirmed in an independent cohort comprising 359 patients receiving up-front IGRT (71%) or LDR-BT (29%) and followed for a median of 9 (IQR 3.1-7.5) years. There was no difference in the disease-specific outcomes (bRFR, mFR) between the 2 cohorts (Gray's P value of .257 and .934, respectively). In multivariate analyses, timing of radical radiation therapy (deferred vs up-front) was not correlated to biochemical relapse or metastases occurrence. Conclusions Curative-intent radiation therapy (ie, dose-escalated IGRT or LDR-BT) after a period of AS renders excellent oncologic outcomes at 5 years. Deferring radical therapy after a period of AS does not seem to result in inferior oncologic outcomes compared with patients with similar risk characteristics undergoing up-front treatment. [ABSTRACT FROM AUTHOR]

Purpose: Current guideline recommends a uniform method of delineation of subclinical disease within the primary clinical target volume (CTVp) for all stages of nasopharyngeal carcinoma (NPC). We performed a prospective observational study to investigate the outcomes with a reduced CTVp and radiation dose for early-stage NPC.Methods and Materials: Patients with newly diagnosed, biopsy-proven World Health Organization type II-III and American Joint Committee on Cancer/Union for International Cancer Control sixth edition stage T1-2N0-1 disease were enrolled. All patients were treated with intensity modulated radiation therapy alone. We categorized CTVp into CTVp1 (high risk) and CTVp2 (low risk). CTVp1 comprised of gross tumor (on magnetic resonance imaging or contrast-enhanced computed tomography) plus a 5-mm margin (3-mm posteriorly) and was prescribed to 60 Gy in 30 fractions (fr). CTVp2 was generated from CTVp1 plus a 5-mm margin (3 mm posteriorly), excluding the maxillary and cavernous sinuses, and was prescribed to 54 Gy in 30 fr. The prescribed doses to the primary and nodal gross tumor volume (GTVp and GTVn) were 68 Gy in 30 fr and 60 to 66 Gy in 30 fr, respectively. Primary endpoint was local recurrence-free survival. This study was registered in ClinicalTrials.gov, number NCT03839602.Results: From May 2001 to August 2006, 103 patients were recruited and completed IMRT. With a median follow-up of 15.2 years (range, 2.1-18.1 years), only 1 patient had local failure. Ten-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival were 90.3%, 88.3%, 90.3%, and 91.2%, respectively. Among late IMRT-related adverse events, we recorded 2 patients with G1 cranial nerve injury, 3 patients with G3 hearing loss, and 3 patients with G3 subcutaneous fibrosis. No patients had temporal lobe necrosis, brain stem injury, or trismus.Conclusions: Decreased CTV margins and radiation doses can achieve long-term tumor control with mild late toxicities for patients with early-stage NPC. [ABSTRACT FROM AUTHOR]

Purpose: The National Comprehensive Cancer Network (NCCN) has recently endorsed the stratification of intermediate-risk prostate cancer (IR-PCa) into favorable and unfavorable subgroups and recommend the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) for unfavorable IR-PCa. Recently, more accurate prognostication was demonstrated by integrating a 22-feature genomic classifier (GC) to the NCCN stratification system. Here, we test the utility of the GC to better identify patients with IR-PCa who are sufficiently treated by RT alone.Methods and Materials: We identified a novel cohort comprising 121 patients with IR-PCa treated with dose-escalated image guided RT (78 Gy in 39 fractions) without ADT. GC scores were derived from tumors sampled in diagnostic biopsies. Multivariable analyses, including both NCCN subclassification and GC scores, were performed for biochemical failure (prostate-specific antigen nadir + 2 ng/mL) and metastasis occurrence.Results: By NCCN subclassification, 33 (27.3%) and 87 (71.9%) of men were classified as having favorable and unfavorable IR-PCa, respectively (1 case unclassifiable). GC scores were high in 3 favorable IR-PCa and low in 60 unfavorable IR-PCa. Higher GC scores, but not NCCN risk subgroups, were associated with biochemical relapse (hazard ratio, 1.36; 95% confidence interval [CI], 1.09-1.71] per 10% increase; P = .007) and metastasis (hazard ratio, 2.05; 95% CI, 1.24-4.24; P = .004). GC predicted biochemical failure at 5 years (area under the curve, 0.78; 95% CI, 0.59-0.91), and the combinatorial NCCN + GC model significantly outperformed the NCCN alone model for predicting early-onset metastasis (area under the curve for 5-year metastasis of 0.89 vs 0.86 [GC alone] vs 0.54 [NCCN alone]).Conclusions: We demonstrated the accuracy of the GC for predicting disease recurrence in IR-PCa treated with dose-escalated image guided RT alone. Our findings highlight the need to evaluate this GC in a prospective clinical trial investigating the role of ADT-RT in clinicogenomic-defined IR-PCa subgroups. [ABSTRACT FROM AUTHOR]