Limited-stage Diffuse Large B-cell Lymphoma

DLBCL, the most common lymphoma subtype, is localized in 25-30% of patients. Prognosis in patients with limited-stage DLBCL (LS-DLBCL) is excellent with 10-year overall survival of at least 70-80%. Improved insights into the disease biology, the availability of positron-emission tomography (PET) scans and recent dedicated clinical trials within this unique population, have led to evolving treatment paradigms. However, no standard definition of LS-DLBCL exists, and while generally defined as Ann Arbor stages I-II disease with largest mass size <10cm in diameter, variations across studies cause challenges in interpretation. Similar to advanced-stage disease, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy forms the basis of treatment, with combined modality therapy including 3 cycles of systemic treatment and involved-site radiation therapy being a predominant historical standard. Yet the well-described continuous risk of relapse beyond 5 years and established late complications of radiotherapy have challenged previous strategies. More rigorous baseline staging and response assessment with PET may improve decision making. Recent clinical studies have focused on minimizing toxicities while maximizing disease outcomes using strategies such as abbreviated immunochemotherapy alone and PET-adapted radiotherapy delivery. This comprehensive review provides an update of recent literature with recommendations for integration into clinical practice for LS-DLBCL patients.

Randomized Phase II Study of PET Response–Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial

PURPOSE To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma. METHODS After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy. RESULTS Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached. CONCLUSION Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.

Metastatic colorectal cancer. Evolution of treatment strategies: surgeons’ point of view

This article explores evolution of treatment options in colorectal cancer with synchronous metastatic disease, role of surgical approach on different stages of combined‑modality therapy, including “liver first” strategy. Prospects of perioperative and neoadjuvant polychemotherapy in patients with colorectal cancer with synchronous distant metastases to liver, data on possibility of using radiation therapy in treatment of primary tumor and liver metastases, as well as risks and benefits of this approach and available clinical research data are analyzed.

Molecular Mechanisms and Current Pharmacotherapy of Peyronie’s Disease: A Review

Peyronie’s disease (PD) is a localized fibrotic lesion of the penis that has adverse effects on men’s health. In this review, we summarized the molecular mechanisms and pharmacotherapies of PD. A literature search was conducted using PubMed and Cochrane Library during 2001–2020. Although no oral or topical medication demonstrated efficacy in monotherapy of PD, several intralesional medications have yielded promising results. Currently, the effective strategy in management of PD should be combined modality therapy, including but not limited to pharmacotherapy, mechanical therapy, and psychotherapy. Meanwhile, basic research is still necessary to facilitate the development of novel and more reliable treatments. In future, more attention should be given simultaneously to epigenetic changes, inflammatory cytokines, the abnormal wound-healing process, and profibrotic and anti-fibrotic factors to provide more options for this refractory disease.

A cost-effectiveness analysis of front-line treatment strategies in early stage follicular lymphoma

Recent data suggests the use of radiotherapy alone (RT) in Early-Stage Follicular Lymphoma is declining. Cost-effectiveness analysis of treatments has not been performed. We constructed a partitioning model (15-year horizon) to compare RT, combined-modality therapy (CMT) and immunochemotherapy with rituximab maintenance (ICT+RM) from a PET-staged cohort from the Australian Lymphoma Alliance. Lifetime direct health care costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. AUD $75,000 was defined as the willingness-to-pay threshold (WTP). The direct healthcare costs were: RT $12,791, CMT $29,391 and ICT+RM $42,644. Compared with RT, CMT demonstrated minimal improvement in QALYs (+0.01) and an ICER well above the WTP threshold ($1,535,488). Compared with RT, ICT+RM demonstrated an improvement in QALYs (+0.41) with an ICER of $73,319. Modelling a 25% cost reduction with a rituximab biosimilar led to further ICER reductions with ICT+RM ($52,476). ICT+RM is cost-effective in early stage FL from the Australian taxpayer perspective.

Diagnosis and Management of Radiation Necrosis in Patients with Brain Metastases and Primary Tumors

The incidence of radiation necrosis has increased secondary to combined modality therapy for brain tumors and stereotactic radiosurgery. The pathology of progressive brain radiation necrosis (RN) primarily includes inflammation and angiogenesis in which cytokines, chemokines, and vascular endothelial growth factors are upregulated. Combined multiparametric imaging, including lesional metabolism, spectroscopy, and blood flow, could enhance diagnostic accuracy compared with a single imaging study. Nevertheless, a substantial risk of bias restricts firm conclusions about the best imaging technique for diagnosing brain RN. Bevacizumab shows promising results of improving radiographic edema and post-gadolinium enhancement with associated symptomatic improvement. However, this was based on small double-blinded randomized controlled trials, which introduces a high risk of bias due to the small sample size despite the high-quality trial design. Edaravone combined with corticosteroids also resulted in a more significant reduction in radiographic edema than corticosteroids alone but had no impact on reducing the enhancing lesion. There is a great need for further prospective randomized controlled trials (RCTs) to treat brain RN.

Combined-Modality Therapy for Locally Advanced Esophageal Cancer in Endemic Region of Turkey: A Single-Center Multimodal Experience

Background: Esophageal cancer (EC) is known as the most common cancer around the world. The evidence supports that preoperative chemoradiotherapy (CRT) improves resectability and survival in locally advanced EC patients. Objectives: The current study aimed to evaluate the results of treatment in patients suffering from EC in an endemic region. Methods: In this study, a total of 180 EC patients treated with curative radiotherapy (RT) were retrospectively evaluated. Primary tumor location, histopathological characteristics, tumor, nodes, and metastases (TNM) status, gender, age, treatment modalities, and survival period were also assessed. The effects of prognostic factors on the survival rate were evaluated using single variable analysis. Results: The median time of follow-up was reported as 22.9 months (range: 6-115 months). After 1-, 3-, and 5-year follow-up, the rates of survival were calculated at 86.6%, 46.6%, and 32.5%, respectively. The present study was conducted on 77 (42.8%) male and 103 (57.2%) female patients (mean age: 60±12 years). In histopathological assessment, squamous cell carcinoma was the most frequent diagnosis (n=156; -86.6%). The clinical stages were reported as II in 36.6% (n=66), IIIa in 23.4% (n=42), IIIb in 15.5% (n=28), and IIIc in 24.5% (n=44) of the patients. In this study, 54 (25%) patients were treated with definitive RT, 33 patients (18.3%) with postoperative adjuvant CRT or RT, 59 patients (32.8%) with preoperative CRT or RT, and 43 patients (23.9%) with definitive CRT. The Eastern Cooperative Oncology Group (ECOG) performance status was observed to be ECOG 0 in 51 subjects (28.4%), ECOG 1 in 95 subjects (52.8%), and ECOG 2 in 34 subjects (18.8%). Moreover, 96 (53.4%) and 84 (46.6%) patients received conventional and conformal RT, respectively. The median time of overall survival (OS) was reported as 29 months. In univariate analysis, the T stage (P=0.041), N stage (P=0.033), TNM staging (P=0.00), and concomitant CRT (0.001) were prognostic factors affecting median OS time. Concomitant CRT (hazard ratio [HR]: 0.513; 95% CI: 0.337-0.779; P=0.002) and TNM stage (HR: 2.265; 95% CI: 1.409-3.641) were observed statistically significant as independent prognostic factors of mortality in multivariate analysis. Conclusions: Long-term survival using combined-modality therapy was demonstrated in patients with locally advanced EC. Furthermore, based on the results of multivariate analysis, TNM stage and concomitant CRT were considered independent prognostic factors of mortality.