Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial.

BACKGROUND: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. METHODS: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. RESULTS: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). CONCLUSIONS: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

Selected Patients With Peritoneal Metastases From Breast Cancer May Benefit From Cytoreductive Surgery: The Results of a Multicenter Survey.

Background: Even though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments. Methods: We considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model. Results: Of the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype. Conclusions: The improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.

Diagnostic and therapeutic algorithm for colorectal peritoneal metastases. A consensus of the peritoneal surface malignancies onco-team of the Italian society of surgical oncology.

AIM: the surgical workup for colorectal cancer peritoneal metastases (CRCPM) is complex and should be managed in specialized centers. Diagnostic and therapeutic algorithms (DTA) have been proposed to balance optimal patients management and correct use of resources. Aim of this study was to establish a consensus on DTA for CRCPM patients in Italy. METHOD: a panel of 18 delegated members of centers afferent to Peritoneal Surface Malignancies Onco-team of the Italian Society of Surgical Oncology was established. A list of statements regarding the DTA of patients with CRCPM was prepared according to different activities and decision-making nodes with a defined entry and exit point. Consensus was obtained through RAND UCLA methodology. RESULTS: two different DTA were defined and approved according to the modality of presentation of CRCPM (synchronous and metachronous). A consensus was also obtained on 17 of the 19 statements related to DTA. CONCLUSION: a shared model of DTA is now available for healthcare providers to monitor appropriateness in diagnosis and treatment of patients with isolated peritoneal metastases from CRC.

Review. Current role and future perspectives of hyperthermia for prostate cancer treatment.

Prostate cancer is the second most common cause of death in men. Between 10%-60% of patients experience biochemical recurrence associated with treatment failure. No consensus on optimal therapy for advanced prostate cancer exists and even though hormonal therapy and radiotherapy are standards, different groups have included hyperthermia associated with radiotherapy to increase its efficacy. We have tried to analyze these studies to evaluate if this association can ameliorate the therapy in the advanced disease state. From the analysis of these studies, it appears that no amelioration can be obtained adding hyperthermia and the principal cause of this failure appears to be due to the incorrect timing of hyperthermia application and probably the abrogation of androgen receptor expression in androgen-dependent cells.

Hyperthermia and immunity. A brief overview.

After many years, hyperthermia (HT) is experiencing a new resurgence as seen by the positive results of many randomized trials all over the world. Tumour immunity similarly is suggested as the fourth modality of therapy for metastatic tumours from renal carcinoma and melanoma. An overwhelming amount of data from animal models and human patients indicate that whole body and locoregional hyperthermia exerts many biological and therapeutic effects on immune competent cells and cytokines. Among these effects, hyperthermia has recently been demonstrated to enhance the antigen presentation and consequently the activity of dendritic cells. This improvement is obtained through several mechanisms: a) increased lymphocyte recruitment and trafficking into the tumour area; b) increased immunogenicity of heat treated tumour cells; and c) increased production of the heat-shock proteins and costimulatory molecules. The effects and mechanisms of HT on immunity, lymphocyte recruitment and dendritic cell stimulation by heat shock proteins are reviewed here. Moreover the use of HT as an innate immunity booster in association with biological response modifiers is suggested.

Thoracic stop-flow perfusion in the treatment of refractory malignant pleural mesothelioma: a phase I-II evaluation/trial.

Malignant pleural mesothelioma (MPM) is an aggressive treatment-resistant tumor with a median survival from diagnosis of 12 months. Although multimodality protocols that combine aggressive surgery and adjuvant chemotherapy or radiotherapy have shown improved survival in selected cases, the majority of patients with MPM are not suitable for radical surgery due to advanced stage and comorbid medical illness. For these patients combination chemotherapy with Pemetrex and Cisplatin should be considered for first line palliative chemotherapy. The therapeutic options available to patients with MPM resistant or refractory to systemic chemotherapy are very limited. Thoracic "stop-flow" perfusion (TSP) is a semi-invasive loco-regional drug delivery system that, limiting the circulation to the thorax during the anticancer agent's infusion, claims the advantage of reaching high drug concentration at the tumor site while maintaining a low systemic toxicity. The aim of this phase I-II study was to evaluate the toxicity profile and efficacy of two different platinum-based combined regimens--cisplatin plus mitomycin-C (MMC) and cisplatin plus melphalan (L-PAM)--administered using TSP technique in patients with advanced or recurrent MPM who had refractory disease after systemic first line chemotherapy. Patients with histologically proven unresectable stage II-III MPM entered this trial. Between January 1995 and December 2001, 27 patients were enrolled in the study and submitted to TSP using the two different chemotherapy cisplatin based regimens: 12 patients received cisplatin 100 mg/m2 plus MMC 20 mg/m2 (MMC arm) and 15 cisplatin 100 mg/m2 plus L-PAM 50 mg/m2 (L-PAM arm). Objective responses were assessed by CT-scan 30 and 60 days after the end of treatment in all 27 enrolled patients. Two patients (7.4%) achieved a complete response, 2 (7.4%) a partial response and 4 (14.8%) a minor response. The remaining 19 patients (70.3%) showed a stable disease. No patients developed progression of the disease following the first TSP. The overall median time to progression was 8.9 months (range 1-41). The median survival time for all patients from the beginning of regional chemotherapy was 16.6 months, with a 1-year survival rate of 62.9%, a 2-year survival rate of 18.5%, and a 3-year survival rate of 7.4%. Our data show that TSP is a relatively effective second-line treatment in patients with progressive disease after systemic chemotherapy, with a low rate of major complications and treatment-related toxicity.

Radiofrequency ablation of 40 lung neoplasms: preliminary results.

OBJECTIVE: Radiofrequency thermal ablation is a minimally invasive treatment widely used for treatment of liver neoplasms and has also been tested on other types of tumor. Few studies have been published regarding the use of radiofrequency thermal ablation in the treatment of lung neoplasms. This study was performed to evaluate the technical feasibility, the safety, and the efficacy of lung radiofrequency thermal ablation. SUBJECTS AND METHODS: Between February 2002 and March 2003, 18 subjects with unresectable lung neoplasms, four of whom had primary neoplasms and 14 of whom had metastatic neoplasms, underwent lung radiofrequency ablation. The technique was performed percutaneously using a monopolar cooled-tip electrode needle under CT guidance with the patient under general anesthesia. Patients had no more than three nodules with a total diameter of 10 cm and no evidence of extrathoracic disease. A total of 40 nodules were treated in 24 therapeutic sessions. After treatment, patients underwent follow-up every 3 months by CT and nuclear MRI with gadolinium for a median time of 8 months (range, 2-14 months). RESULTS: No evidence of local relapse was discovered in 94.4% of subjects. The treatment was safe and well tolerated. Complications encountered included massive pneumothorax, which occurred in one subject, requiring pleural drainage. Other complications were moderate pneumothorax (also requiring pleural drainage), cough, fever, slight dyspnea, and pain, but these complications were short in duration and successfully treated. CONCLUSION: Radiofrequency thermal ablation is a promising technique in the treatment of patients with lung neoplasms and has been found to be both safe and technically feasible.