Multimodality Therapy In Patients Research Articles

Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma.

The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.

Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports

ABSTRACT Introduction The growing body of real-life data on maintenance treatment with durvalumab suggests that immunological markers of the cancer host interplay may have significant effects on the efficacy of multimodal therapy in patients with unresectable stage III NSCLC. Areas covered We summarize real-world clinical data regarding this new tri-modal approach and report on potential biomarker landscape. Expert opinion The obvious question posed in this context of a very heterogeneous inoperable stage III NSCLC disease is: How can we augment an ability to predict checkpoint inhibition success or failure? Which tools and biomarkers, which clinical metadata and genetic background are relevant and feasible? No single biomarker will ever fully dominate the unresectable stage III NSCLC space, so we advocate multilevel and multivariate analysis of biomarkers. In this particular opinion piece, we explore the impact of PD-L1 expression on tumor cells, neutrophil-to-lymphocyte ratio, EGFR and STK11 mutational status, interferon-gamma signature, and tumor-infiltrating lymphocytes among others.

Prognostic Factors and Clinical Outcomes in Extraskeletal Ewing Sarcoma: A Cohort Study.

Extraskeletal Ewing sarcoma (ESE) is a lesser-known, rarer counterpart of Ewing sarcoma of bone. This single-center study sought to evaluate the prognosticators and outcomes following multimodality therapy in patients with ESE. Forty-seven patients with ESE, treated between 2013 and 2018 with a standardized protocol and multimodality therapy using established doxorubicin-based regimens, were followed-up to assess outcomes. Median age at diagnosis was 20 (range 7-56) years, and 57.4% were male. Median tumor size was 7 (range 2-21) cm. The symptom-duration ranged from 1 to 8 (median 4) months. Tumor-site was trunkal in 61.7%, extremity in 23.4%, and head and neck 14.9%. Of the 35 patients with nonmetastatic disease at presentation, 13 underwent upfront surgery. The rest received chemotherapy followed by local treatment, which was surgical in 15 and radiotherapy in 5. At median follow-up of 24 (range 5-98) months, 55.3% patients had experienced events, and 29.8% had diedof progressive disease. Three-year event-free survival was 41.1%, and overall survival was 53%. On univariate analysis, trunkal location, upfront surgery, and positive surgical margins were associated with inferior EFS. Trunkal tumors and upfront surgery were alsoassociated with poorer OS. On multivariate analysis, trunkal location and margin-positive resections retained statistical significance for adverse EFS. Unless clearly resectable upfront, ESE should be downstaged with chemotherapy before local treatment. A margin-negative resection should be the objective when performing surgery. Definitive radiotherapy is an alternative in tumors not amenable for complete excision or when anticipated postoperative morbidity precludes radical surgery.

Role of tumor reduction surgery in multimodality therapy for advanced thymoma—case series

Background: Optimal treatment for advanced thymoma remains controversial. This study aimed to elucidate the effectiveness of intended tumor reduction in multimodality therapy for patients with an unresectable thymoma.

Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database.

Factors associated with refusal of multimodality therapy in patients with localized esophageal adenocarcinoma (EA) remain unknown. We hypothesized that sociodemographic disparities affect decision to pursue optimal trimodally therapy for patients with EA. NCDB for esophageal cancer (2004-2017) was utilized. Included were patients diagnosed with cT3-T4 cN0 or cTany N1-3 EA of the mid-lower esophagus. Annual institutional esophagectomy volumes were categorized as low (<20/year) and high (≥20/year). Conditional logistic regression was used to identify predictors of refusal of offered treatment. Kaplan Meier method was used to compare survival. 13091 patients met selection criteria, mean age was 62.4 ± 9.6 years and 11581 (88.5%) were males. 633 (4.8%) patients refused at least one component of recommended treatment (chemotherapy, radiation, and esophagectomy), most commonly refusal of surgery (N = 554, 4.2%). On multivariable analysis, factors predictive of treatment refusal included older age, female gender, black race, no insurance, low income (below poverty), mid-esophageal tumors, and treatment at low-volume centers. Patients who were recommended treatment but refused had significantly worse survival than those who adhered to treatment (median 23.1 ± 1.1 vs. 32.1 ± 1.2months; P < .001). In this study, sociodemographic disparities and center volume were among factors predictive of therapy refusal in patients with localized esophageal adenocarcinoma. While understanding potential reasons for treatment refusal is critical, this data suggests that socioeconomic variables may drive patient decisions.

Multimodality Therapy in Patients With Primary Pericardial Mesothelioma

IntroductionPrimary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy. MethodsPatients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis. ResultsThe median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21–71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not. ConclusionsPPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.

Differences in receipt of multimodality therapy by race, insurance status, and socioeconomic disadvantage in patients with resected pancreatic cancer.

Background and MethodsRacial and socioeconomic disparities in receipt of adjuvant chemotherapy affect patients with pancreatic cancer. However, differences in receipt of neoadjuvant chemotherapy among patients undergoing resection are not well‐understood. A retrospective cross‐sectional cohort of patients with resected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified from the National Cancer Database (2014–2017). Outcomes included receipt of neoadjuvant versus adjuvant chemotherapy, or receipt of either, defined as multimodality therapy and were assessed by univariate and multivariate analysis.ResultsOf 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624 (49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received no chemotherapy. On multivariable analysis, Black patients had lower odds of neoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI: 0.67–0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95% CI: 0.77–1.03). Patients with Medicaid or no insurance, low educational attainment, or low median income had significantly lower odds of receiving neoadjuvant chemotherapy or multimodality therapy.ConclusionsRacial and socioeconomic disparities persist in receipt of neoadjuvant and multimodality therapy in patients with resected pancreatic adenocarcinoma.DiscussionPolicy and interventional implementations are needed to bridge the continued socioeconomic and racial disparity gap in pancreatic cancer care.

Contemporary Outcomes After Multimodality Therapy in Patients With Breast Cancer Presenting With Ipsilateral Supraclavicular Node Involvement

PurposePatients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined. Methods and MaterialsWe reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed. ResultsData from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus <60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%. ConclusionsIn one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment.

Extracorporeal photopheresis and multimodality therapy in patients with T-cell cutaneous lymphomas: Real-life experience in Argentina.

Extracorporeal photopheresis (ECP) as a part of multimodality therapy, is one of the treatments for Sézary syndrome (SS) and advanced stage mycosis fungoides (MF). This study aims to describe cutaneous and peripheral blood responses of patients with MF and SS who received multimodality therapy. In this cross-sectional retrospective study, patients with MF or SS who received ECP treatment in combination with at least one additional systemic treatment between 2011 and 2018 were included. ECP consisted of a two-session cycle every 2 to 4 weeks. Cutaneous and blood responses were evaluated with updated criteria. Twenty-eight patients (11 (39%) with MF and 17 (51%) with SS) were included. Their median age at diagnosis was 63 (57-67) years. The median number of treatments before ECP was 2 (1-3). Seven out of 11 patients with MF (63%) underwent an assessment of cutaneous response. Five patients (70%) presented a partial response; 1 (15%), stable disease, and 1 (15%) progressive disease. Thirteen of the 17 patients with SS (76%) underwent evaluation. One patient (8%) presented a complete cutaneous response; 6 (46%), a partial response; 5 (38%), stable disease; and 1 (8%), progressive disease. None of them relapsed during the study period in both groups. No ECP-related adverse effects occurred during the study. Most patients with SS and MF who underwent multimodality therapy with ECP had favorable cutaneous and blood response. It is safe to combine ECP with other treatments. Studies with large numbers of patients are necessary to assess the effects of ECP on patient survival.

RANDOMIZED STUDY OF INDEX SCORE INDICATORS IN PATIENTS WITH CHRONIC PERIODONTITIS IN THE CHUVASH REPUBLIC

The aim of this work was to determine the values of plaque accumulation indices and oral hygiene indices, to conduct a comparative assessment before the start of multimodality therapy in patients with mild and moderate parodontitis and after its completion among the adult population of the Chuvash Republic. The study of index evaluation values of 146 patients aged 33–62 years with a diagnosis "chronic generalized parodontitis of mild and moderate severity" was conducted. The age range was determined by the criteria for dividing the age groups according to WHO data – early adult (25–35 years), middle adult (36–45 years), late adult (46-60 years). The examination was carried out according to standard clinical methods of simplified oral hygiene index OHI-s (according to Green – Vermillion), dental plaque hygiene index (PI) Silness-Loe (1964), evaluation of the state of periodontal tissues PI (by Russel). The authors present the criteria for evaluating the indices before the start of standard treatment and after its completion for all the studied patients and in groups with mild and moderate severity of chronic generalized parodontitis. The authors give as well a comparative analysis of the patients’ index assessment depending on the severity of the disease, the dynamics of the infection resolution in groups with different degrees of of parodontitis severity.

Impact of Treatment Sequencing on Survival for Patients with Locally Advanced Gastric Cancer.

Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered. Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S). One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p < 0.001). At a median follow-up of 37months, survival rates on an intention-to-treat basis with TNT + S, Periop, and S + Adj were 52.6%, 59.4%, and 45.3%, respectively. Regimen and completion of MMT significantly affected overall mortality risk. Compared with Periop, TNT + S had similar mortality risk (hazard ratio [HR] 1.28, p = 0.421), whereas S + Adj had increased mortality risk (HR 1.64, p = 0.027). The choice of treatment sequencing has a major impact on completion rates of multimodal therapy in patients with locally advanced gastric cancer. Less than 50% of patients treated with upfront surgery or perioperative chemotherapy receive all intended therapies. TNT has higher intended therapy completion rates and comparable survival compared with perioperative therapy in our data. Further prospective investigations of TNT are warranted.

Multimodal Therapy for Patients with High-Grade, High-Risk Prostate Cancer with Long-Term Follow-up

High risk prostate cancer requires a multimodal approach to treatment. Surgery has played an increasing role for these patients although long-term follow-up and experience with neoadjuvant therapy, a basic tenet of cancer treatment, remains limited. Here we report our experience with neoadjuvant hormonal ablation followed by surgery and postoperative radiation with greater than 20-year follow-up. From 1990-2012, 82 patients with clinically organ-confined prostate cancer and 10 years median follow-up underwent multimodal therapy (MMT) consisting of neoadjuvant hormonal ablation followed by radical retropubic prostatectomy and postoperative radiation. High-risk prostate cancer was defined preoperatively as Gleason Score 8-10 or PSA>20. Patients with negative surgical margins were observed initially and treated with salvage XRT in the instance of recurrence. The MMT protocol was well tolerated in all 82 patients with no treatment-related discontinuation of therapy. Final surgical pathology revealed stage pT3-T4 in 58/82 (71%) and nodal involvement in 7/82 (9%). Distant metastatic disease was identified in 10/82 patients (12%). For patients undergoing MMT at 10, 15 and 20 years, cancer-specific survival was 78/82 (95%), 77 /82 (94%) and 77/82 (94%), overall survival was 68/82 (83%), 66/82 (80%) and 60/82 (73%), and biochemical recurrence was 61/82 (74%), 51/82 (62%) and 35/82 (43%). These findings establish the MMT protocol as an effective treatment strategy for high-risk prostate cancer with excellent long-term cancer-specific survival. Recurrence occurring primarily as a rising PSA as opposed to distant metastatic disease suggests limited morbidity as well among patients treated with this protocol.

Parotid sparing and quality of life in long-term survivors of locally advanced head and neck cancer after intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) enables radiation oncologists to optimally spare organs at risk while achieving homogeneous dose distribution in the target volume. Despite great advances in technology, xerostomia is one of the most detrimental long-term side effects after multimodal therapy in patients with locally advanced head and neck cancer (HNC). This prospective observational study examines the effect of parotid sparing on quality of life in long-term survivors. A total of 138patients were grouped into unilateral (n = 75) and bilateral (n = 63) parotid sparing IMRT and questioned at 3, 24, and 60-month follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Treatment-related toxicity was scored according to the RTOG/EORTC toxicity criteria. Patients' QoL24 and 60months after IMRT was analyzed by ANCOVA using baseline QoL (3months after IMRT) as acovariate. Patients with bilateral and unilateral parotid-sparing IMRT surviving 60months experience similar acute and late side effects and similar changes in QoL. Three months after IMRT, physical and emotional function as well as fatigue, nausea and vomiting, pain, dyspnea, and financial problems are below (function scales) or above (symptom scales) the threshold of clinical importance. In both groups, symptom burden (EORTC H&N35) is high independent of parotid sparing 3months after IMRT and decreases over time in asimilar pattern. Pain and financial function remain burdensome throughout. Long-term HNC survivors show asimilar treatment-related toxicity profile independent of unilateral vs. bilateral parotid-sparing IMRT. Sparing one or both parotids had no effect on global QoL nor on the magnitude of changes in function and symptom scales over the observation period of 60months. The financial impact of the disease and its detrimental effect on long-term QoL pose an additional risk to unmet needs in this special patient population. These results suggest that long-term survivors need and most likely will benefit from early medical intervention and support within survivorship programs.

ASO Author Reflections: Multimodality Therapy for Patients with Pancreatic Cancer: Neoadjuvant Therapy for All?

ASO Author Reflections: Multimodality Therapy for Patients with Pancreatic Cancer: Neoadjuvant Therapy for All?

Role of Serum Carcinoma Embryonic Antigen (CEA) Level in Localized Pancreatic Adenocarcinoma: CEA Level Before Operation is a Significant Prognostic Indicator in Patients With Locally Advanced Pancreatic Cancer Treated With Neoadjuvant Therapy Followed by Surgical Resection: A Retrospective Analysis.

The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

Nutrition update in gastric cancer surgery.

Patients with gastric cancer are often malnourished during tumor progression. Malnutrition is a risk factor for postoperative complications and a poor prognosis. Early evaluation and management of nutrition can improve these outcomes. Various combined indices in which albumin is the primary component are used to evaluate the nutritional status, including the Prognostic Nutritional Index, Glasgow Prognostic Score, and Controlling Nutritional Status score. Both the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism guidelines recommend immediate and early oral/enteral nutrition. However, few reports have described the additional effects of preoperative immunonutrition on clinical outcomes of gastric cancer surgery. Gastrectomy types and reconstruction methods that consider the postoperative nutritional status have been used when oncologically acceptable. Total gastrectomy has recently tended to be avoided because of its negative impact on nutritional status. New findings obtained from the emergence of continuous glucose measurement, such as glucose fluctuation and nocturnal hypoglycemia, may affect nutritional management after gastrectomy. Some prospective clinical studies on perioperative nutritional intervention have set postoperative body weight loss as a primary endpoint. It seems important to continue oral nutritional supplement, even in small doses, to reduce body weight loss after gastrectomy. Evidence generated by prospective, well‐developed randomized controlled studies must be disseminated so that nutritional therapy is widely recognized as an important multimodal therapy in patients undergoing gastric cancer surgery.

Phase II trial of durvalumab plus tremelimumab with concurrent radiotherapy as bladder-sparing therapy in patients with localized muscle invasive bladder cancer: A SOGUG study.

TPS5097 Background: Several studies have shown that long-term bladder preservation is feasible in selected patients with muscle-invasive bladder cancer, using a multimodal treatment, including transurethral resection (TUR), radiotherapy and chemotherapy. Durvalumab, a fully human monoclonal antibody against PD-L1, has shown activity in patients with advanced pretreated urothelial cancer. A preclinical study showed that the combination of radiation, anti-CTLA4 and anti-PD-L1 overcome- adaptive immune resistance and has superior activity than either therapy alone (Twyman-Saint Victor et al. Nature 2015). The purpose of the present study is to explore feasibility, toxicity and activity in terms of response and bladder preservation of the integration of TUR, immune double checkpoint inhibition with durvalumab and tremelimumab (a fully human monoclonal antibody against CTLA-4), and radiotherapy in the treatment of localized muscle-invasive. Methods: This is a multicenter prospective phase II study of multimodal therapy in patients with localized urothelial carcinoma of the bladder in clinical stages T2-4a N0 M0, ECOG 0- 1, without contraindications to immunotherapy, who either wish for bladder preservation or are ineligible for cystectomy. The primary endpoint is pathological response (≤T1) at post-treatment biopsy. A 2-stage sequential design (response rate P0=5, P1=0.7, α=0.10, β=0.20) requires at least 6 responses in the first 12 pts to expand to a second cohort of 20 patients. The treatment consists of initial TUR of the tumor, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for 3 doses. Normofractionated external-beam radiotherapy is started 2 weeks later, at doses of 46 Gy to the minor pelvis and 64-66 Gy to the bladder. Patients with pathological response will be candidates to bladder preservation, whereas those with residual muscle invasive tumor will be candidates to salvage cystectomy. At present time, prespecified activity goal for the first stage of accrual was met; second stage accrual began in December 2019. Clinical trial information: NCT03702179 .

Multimodality Therapy of Patients with Refractory Meningiomas.

Recurrent and refractory meningiomas are a clinical challenge and treatment at the time of recurrence is not well delineated. Treatment with surgery and/or radiation remain the mainstay, but each has their limitations and risks. The search for an adjuvant systemic therapy continues and as many of the initially promising approaches have not had reproducible responses. Bevacizumab has shown some efficacy in controlling recurrent disease and could be useful in disease that is multifocal or in close proximity to critical structures. Other targeted therapies, as well as immunotherapy, are being studied and trials are in development. Though we are hopeful that these novel therapies will benefit patients with refractory meningiomas, we approach them with some trepidation. This is due to prior failures of immunotherapy and targeted therapy in central nervous system disease. In addition, there is known difficulty in developing trials and assessing response with these slow-growing tumors.

Evaluation of influence of the UPOINT-guided multimodal therapy in men with chronic prostatitis/chronic pelvic pain syndrome on dynamic values NIH-CPSI: a prospective, controlled, comparative study.

Background:The aim of this work was to evaluate the influence of UPOINT-guided (Urinary, Psychosocial, Organ-specific, Infection, Neurologic/systemic, Tenderness of skeletal muscles) multimodal therapy in patients with chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) on the dynamic values of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score.Patients and methods:In our study we investigated 110 patients aged 26–68 years with CP/CPPS. We performed digital rectal examination (DRE), pre- and post-massage test (PPMT) urine culture, urine analysis, transrectal ultrasound investigation of prostate, antibiotic susceptibility testing. We divided the patients into the intervention group and the control group which was followed up without any therapy. For the intervention group we offered multimodal therapy based on each predominated positive phenotype. For the urinary phenotype, patients in intervention group received 10 mg alfuzosin. For organ-specific and tenderness domains, the patients of the intervention group received 63 mg Cernilton and 1 g Quercetin. For infection control, the patients of the intervention group received antimicrobial agents according to the results of the post-massage urine culture, antibiotic susceptibility testing and a high level of contamination >105 colony-forming units (CFU)/ml. Microbiological assessment of PPMT urine culture was conducted with aerobic and anaerobic methods of cultivationResults:The 110 patients had an average age of 43.9 ± 11.1 years and a median duration of symptoms of 6.21 ± 1.8 months. Of these, 11 patients did not complete the trial and therefore in quantitative terms, the distribution of patients was as follows: 54 in the intervention group and 45 in the control group. The average total NIH-CPSI score before treatment was 29.8 ± 6.1 in both groups. The mean NIH-CPSI of the pain, urinary, and quality of life (QOL) subscores before treatment was 15.1 ± 3.0, 7.4 ± 1.4 and 8.1 ± 2.1, respectively in both groups. After 6 weeks the PPMT urine culture of patients of the intervention group showed the absence or low-level contamination of microorganisms. After conducting the treatment, the mean total NIH-CPSI score in the intervention and control groups was 13.9 ± 2.8 (p = 0.025) and 29.8 ± 5.8 (p = 0.18), respectively. The average NIH-CPSI pain subscore in the intervention and control group after treatment was 6.7 ± 1.4 (p = 0.018) and 15.1 ± 2.8 (p = 0.21), respectively. The mean NIH-CPSI urinary subscore after treatment in the intervention and control group was 3.22 ± 1.07 (p = 0.045) and 7.4 ± 1.2 (p = 0.15), respectively. The average NIH-CPSI QOL subscore after treatment in the intervention and control group was 3.87 ± 1.28 (p = 0.015) and 8.1 ± 1.9 (p = 0.35). After multimodal therapy, the prevalence of different UPOINT-positive domains in the patients of both intervention groups did not exceed 14%.Conclusions:The UPOINT clinical phenotypes significantly changed after multimodal treatment, including antibiotics, phytotherapy and α-blockers in patients with CP/CPPS. This combination of treatment showed a decreasing total NIH-CPSI score and an elevation of QOL in patients.

Conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma: where do we stand in 2018?

Abstract Pancreatic ductal adenocarcinoma (PDAC) continues to have a dismal prognosis, with a 5-year survival rate of &lt;5%. Most (70%–80%) patients are classified as unresectable (UR) disease. Recent progress in chemotherapeutic approaches has provided a high response rate and improved short-term survival. Recently, conversion surgery (CS), which is defined as an additional surgery during multimodal therapy in patients with initially UR-PDAC who respond favorably to anti-cancer treatments, has been successfully introduced as a novel treatment option for locally advanced (UR-LA) and metastatic (UR-M) PDAC. Several studies have demonstrated high resectability rates (UR-LA, 20%–57%; UR-M, 2%–24%), high margin-negative resection rates (27%–91%), and high negative lymph node rates (29%–83%) in patients who underwent CS. Most studies also demonstrated acceptable mortality and morbidity. Median survival time (MST) varied between 24.9 and 35.3 months for patients with UR-LA, 19.5 and 64 months for UR-LA/M, and 26 and 56 months for UR-M, which is better than the MST of patients who did not undergo CS. The presence of M disease did not affect survival in patients who underwent CS. However, the actual clinical benefits of resection have not yet been fully investigated. There are still several issues to be resolved in this area. Therefore, sustained efforts to conduct appropriately designed clinical trials for confirming the efficacy of CS in the subset of patients with initially UR-PDAC are warranted.