Palliative Systemic Chemotherapy Research Articles

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)-directed treatment of peritoneal metastasis in end-stage colo-rectal cancer patients.

BackgroundPressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) represents a novel approach to intraperitoneal chemotherapy. Hereby results, obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from colorectal cancer (CRC), are presented.MethodsData from CRC patients (n = 24) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 trials are reported. Oxaliplatin 92 mg/m2 was administered at 4-6-week intervals. A CE certified nebulizer was used to aerosolize the chemotherapeutics. Outcome criteria were objective tumor response, survival and adverse events.ResultsRetrospective analysis of 74 PIPAC procedures carried out in 24 consecutive patients with PM from CRC included from October 2015 to February 2019. Five patients had still the primary tumor in situ, and 22 patients had received palliative systemic chemotherapy. Nineteen patients completed more than two PIPAC procedures, and objective tumor response according to the histological Peritoneal Regression Grading Score (PRGS) was observed in 67% of the patients, while 21% had stable disease. Four patients (21%) had complete response (mean PRGS = 1 and negative cytology). We recorded a median survival of 37.6 (range 7.3–48.9) months from the time of PM diagnosis, whereas it was 20.5 (range 0.13–34.7) months following the first PIPAC session. Minor postoperative complications were noted, and few were considered causally related to the PIPAC treatment. However, two cases of severe postoperative complications were recorded (urosepsis and iatrogenic bowel perforation).ConclusionsPIPAC with low-dose oxaliplatin can induce objective tumor regression in selected patients with advanced PM from colorectal cancer.

Küçük Hücreli Dışı Akciğer Kanserli Kranial Metastaz Gelişen Olgularda Metastazektomi Yapılan ve Sistemik Tedavi Alan Hastaların Retrospektif Değerlendirilmesi

Küçük hücreli dışı akciğer kanseri (KHDAK)’nin en sık metastaz yaptığı organlardan biri beyindir. Beyin metastazı olan hastalar tedavi edilmediğinde ortalama yaşam süresi aylarla sınırlıdır. Bu çalışmanın amacı beyin metastazı yapmış evre 4 KHDAK hastalarda beyin metastazı için cerrahi tedavi uygulamasının onkolojik sonuçlarını göstermektir. Kliniğimizde 2004-2012 yılları arasında KHDAK tanısı konan ve BM nedeniyle cerrahi tedavi uygulanan 59 hastanın verileri prospektif olarak kaydedildi ve retrospektif olarak incelendi. Hastaların cerrahi ve onkolojik sonuçları irdelendi. Sağ kalım süresi beyin metastazı tanısı konulduğu tarih ile ölüm tarihi veya mevcut en son takip arasındaki zaman olarak hesaplandı. Hastaların 51’i erkek, 8’i kadın, ortalama yaş 56.92 (37-81) yıl idi. Cerrahi olarak 55 hastaya total eksizyon, 4 hastaya subtotal eksizyon yapıldı. Ameliyat sonrası mortalite saptanmadı. Patolojik inceleme sonucunda 55 hastada cerrahi sınırlar tümörsüz, 4 hastada ise cerrahi sınır mikroskobik pozitif olarak bildirildi. Ameliyat sonrasında tüm hastalara palyatif kranial radyoterapi ve sistemik kemoterapi verildi. 11 hastaya(%18,6) akciğerdeki primer kitleye kemoradyoterapi verildi. 8 hastaya akciğere yönelik cerrahi lobektomi, 7 hastaya pnömonektomi uygulandı. Medyan genel sağkalım süresi 12,00 (1,0-159,0) aydı. Hastaların 12, 24 ve 60 aylık sağkalım oranları sırasıyla %47.5, %28.8 ve %13.5 olarak bulundu. Üç olguda ise 10 yılın üzerinde genel sağ kalım elde edildi. Beyin metastazı yapmış KHDAK’lu hastalarda kranial metastazektomi hastaların sağkalımına olumlu katkı sağlayabilir.

Glaucoma as the presenting sign of intraocular tumors: beware of the masquerading sign.

To discuss the clinical presentation and management of intraocular tumors masquerading as primary glaucoma or non-tumor-related secondary glaucoma. Retrospective chart review. Ten patients with unsuspected intraocular tumor were referred to glaucoma clinic with a diagnosis of primary glaucoma or non-tumor-related secondary glaucoma. The mean age at referral was 25years (median, 22years; range, 1day to 58years). Referral diagnosis included neovascular glaucoma (n = 6), congenital glaucoma (n = 3), and angle-closure glaucoma (n = 1). The significant clinical signs included corneal edema (n = 3), megalocornea (n = 3), iris neovascularization (n = 4), hyphema (n = 2), and pseudohypopyon (n = 2). The mean interval between the onset of symptoms and the establishment of accurate diagnosis was 4months (median, 3months; range, 0.5-13months). Two patients underwent inadvertent trabeculectomy, and one patient underwent evisceration prior to definitive diagnosis. The final diagnosis included uveal melanocytoma (n = 2), ciliary body medulloepithelioma (n = 2), choroidal melanoma (n = 2), retinoblastoma (n = 1), retinal capillary hemangioblastoma (n = 1), choroidal schwannoma (n = 1), and uveal metastasis (n = 1). The treatment modalities included plaque radiotherapy (n = 1), enucleation (n = 6), palliative systemic chemotherapy (n = 1), a combination of enucleation, systemic chemotherapy, and external beam radiotherapy (n = 1), and one patient was lost to follow-up. There was no evidence of death over a mean follow-up period of 13months (median, 5months; range, 2weeks to 7years). Unilateral raised intraocular pressure, iris neovascularization, or both may be the presenting features of intraocular tumors. High degree of suspicion and a thorough examination reveals the definitive diagnosis.

Opportunity Costs of Receiving Palliative Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma.

The median overall survival (OS) for metastatic pancreatic ductal adenocarcinoma (mPDAC) is < 1 year. Factors that contribute to quality of life during treatment are critical to quantify. One factor-time spent obtaining clinical services-is understudied. We quantified total outpatient time among patients with mPDAC receiving palliative systemic chemotherapy. We conducted a retrospective analysis using four patient-level time measures calculated from the medical record of patients with mPDAC receiving 5-fluorouracil infusion, leucovorin, oxaliplatin, and irinotecan; gemcitabine/nab-paclitaxel; or gemcitabine within the University of Pennsylvania Health System between January 1, 2011 and January 15, 2019. These included the total number of health care encounter days (any day with at least one visit) and total visit time. Total visit time represented the time spent receiving care (care time) plus time spent commuting and waiting for care (noncare time). We performed descriptive statistics on these outpatient time metrics and compared the number of encounter days to OS. A total of 362 patients were identified (median age, 65 years; 52% male; 78% white; 62% received gemcitabine plus nab-paclitaxel). Median OS was 230.5 days (7.6 months), with 79% of patients deceased at the end of follow-up. On average, patients had 22 health care encounter days, accounting for 10% of their total days survived. Median visit time was 4.6 hours, of which 2.5 hours was spent commuting or waiting for care. On average, patients receiving palliative chemotherapy for mPDAC spend 10% of survival time on outpatient health care. More than half of this time is spent commuting and waiting for care. These findings provide an important snapshot of the patient experience during ambulatory care, and efforts to enhance efficiency of care delivery may be warranted.

Palliative systemic chemotherapy with or without pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin (PIPAC C/D) for gastric cancer with peritoneal metastasis: A propensity score analysis.

380 Background: Gastric cancer (GC) with peritoneal metastasis (PM) has a dismal prognosis. Palliative systemic chemotherapy (SC), usually doublet combinations of platinum and fluoropyrimidines, is the standard of care. Pressurized IntraPeritoneal Aerosol Chemotherapy with Cisplatin and Doxorubicin (PIPAC C/D) yields promising results. Here we aimed to compare overall survival (OS) between SC + PIPAC C/D vs. SC alone in patients with PM from GC. Methods: Prospective cohort of 95 consecutive patients with PM from GC treated in palliative intent at our institution from 2010 to 2018. Of these patients, 69 received SC + PIPAC C/D („PIPAC“), 26 SC alone („control“). Choice of treatment was not dictated by medical criteria, but by (non-) availability of the single-use medical devices needed for PIPAC in Russia. All patients received doublet or triplet chemotherapy with platinum together with fluoropyrimidines or capecitabin. A Cox proportional hazard model based on propensity score (PS) was used to assess the effect of PIPAC on OS and account for confounding factors. Results: The HR adjusted for PS for PIPAC vs. control was 0.396 (CI 5- 95% = 0.224-0.700, p-value 0.001). In the simple (unadjusted) Kaplan-Meier, median survival in the control group was 7.0 months (CI: 4.51 - 9.49) and in the PIPAC group 14.0 months (CI: 11.46-16.54). In the control group, all 26 patients died after 1-25 months. In the PIPAC group, 36 of 69 patients died after 4 to 20 months. The longest observed survival time in the PIPAC group was 27 months. Significance for the log-rank test after Mantel-Cox (not adjusted) was p &lt; 0.0001. Conclusions: Compared with SC alone, intensified chemotherapy combining PIPAC C/D and SC doubled OS. These promising results need to be confirmed in a randomized trial.

Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

IntroductionCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a...

Needle-guided ablation of locally advanced pancreatic cancer: cytoreduction or immunomodulation by in vivo vaccination?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a dismal prognosis. About a third of all patients with pancreatic cancer present with locally advanced inoperable disease and are currently designated to palliative systemic chemotherapy. Despite improved chemotherapeutic treatment by the introduction of FOLFIRINOX, median overall survival remains poor at approximately 14 months. Several needle-guided ablative therapies are investigated as treatment option for patients with locally advanced pancreatic cancer (LAPC). This review aims to give an overview of literature of the following needle-guided ablative techniques for the treatment of patients with LAPC: radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation (IRE). The immunomodulatory effects of the ablative techniques in PDAC are also discussed. These effects in combination with immunotherapy may provide an opportunity to enhance clinical efficacy and endow local ablation with systemic tumor control. Especially less immunogenic tumors like PDAC may benefit from this new approach. Preclinical and clinical findings, possible mechanisms of action, and future research directions are addressed.

Therapy and Prophylaxis of Peritoneal Metastases from Colorectal Cancer.

Stage IV colorectal cancer is associated with high mortality, and the prognosis is significantly worse for patients have peritoneal metastases. Peritoneal carcinomatosis from colorectal cancer was considered incurable with an infaust prognosis. Median survival of untreated patients is about 6 months and palliative systemic chemotherapy can prolonge this time up to 20 months. Patients with this disease were previously only surgically treated if they had severe clinical symptoms or complications. This view has changed dramatically over the past 15 years. Aggressive cytoreductive surgery in combination with intraperitoneal chemotherapy may prolong median survival for more than 40 months in selected patients. The Peritoneal Surface Oncology Group International (PSOGI), the international authority on the treatment of peritoneal tumors, recommends cytoreduction with intraperitoneal chemotherapy as the standard of care for selected patients with moderate-to-small volume peritoneal metastases secondary to colorectal cancer. Macroscopic cytoreduction appears to be essential; however, the role of hyperthermic intraperitoneal chemotherapy and the optimal chemotherapeutic agent for intraperitoneal lavage to treat peritoneal metastases from colorectal cancer remain unclear. The results of ongoing and future clinical trials are eagerly awaited.

Palliative chemotherapy in carcinoma nasopharynx.

Introduction:Nasopharyngeal carcinoma is a rare malignancy. We conducted an audit of systemic therapies received in palliative setting in carcinoma nasopharynx and studied their outcomes.Methods:Patients who underwent first-line palliative systemic chemotherapy between January 2014 and April 2017 for carcinoma nasopharynx at the department of medical oncology at authors’ institute were selected for this analysis. Toxicities, responses, progression-free survival (PFS), and overall survival (OS) were analyzed. In addition, a Quality-Adjusted Time without Symptoms or Toxicity analysis with threshold utility analysis was performed.Results:Fifty-one patients were included in this analysis. The indication of palliative chemotherapy was locoregionally recurrent disease in 25 (49.0%) patients and metastatic disease in 26 (51.0%) patients. The overall response rate was 62.0% (n = 33). The median PFS was 225 days (95% confidence interval [CI]: 164–274 days) and median OS was 513 days (95% CI: 286–931 days). The restricted mean TOX state duration was 2.6 days (95% CI: 0.3–4.9), restricted mean TWiST duration was 219.2 days (95% CI: 184.0–254.4), and restricted mean REL duration was 74.3 days (95% CI: 38.1–110.4).Conclusion:Systemic cytotoxic therapy in nasopharyngeal cancers is associated with high response rates and clinically meaningful PFS; with low duration of time spent in adverse events.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

BackgroundAt present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients.The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy.MethodsIn this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression.DiscussionThe PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only.Trial registrationclinicaltrials.gov NCT03348150; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

Metaplastic carcinoma of the breast: Prognosis and response to systemic treatment in metastatic disease.

Metaplastic breast carcinomas (MpBCs) are rare, aggressive breast cancers. Due to the scant literature of this disease most guidelines do not give recommendation for this entity. The aim of the study was to review the clinicopathologic features, treatment, and outcomes of the patients with MpBC treated at our institution. We searched databases for patients with histologically confirmed MpBC from 2002 to 2016. A total of 78 patients with MpBC were included in the study. All histological material was reviewed by an experienced breast pathologist. Most tumors were grade 3 (83%) and triple negative (85%). Eighty-two percent were node negative. Sixty-four percent received adjuvant chemotherapy. The 5-year disease free survival was 63% and 5-year breast cancer specific overall survival was 61%. Tumor size and mixed metaplastic histology were associated with worse outcome in this patient group. One third of the patients (n=28) had metastatic disease at initial presentation or developed metastases at follow-up. The lungs were the most common site of first distant recurrence. Half (n=14) of these patients received palliative chemotherapy. Of those only 6% (n=2) had partial response and 18% had stable disease as best response to treatment. The median overall survival time with metastatic disease was only 3.4months. MpBC is an aggressive type of breast cancer with poor outcome despite low nodal involvement and aggressive local and systemic therapy. Tumor response to palliative systemic chemotherapy remains poor for MpBC patients.

SYSTEMIC CHEMOTHERAPY IN APPENDICEAL ADENOCARCINOMAS WITH PERITONEAL METASTASES. IS IT WORTH IT?

Introduction: The role of systemic chemotherapy (SC) in the management of metastatic appendiceal adenocarcinomas is not defined.Methods: We perform an observational study of patients treated of peritoneal metastases from appendiceal neoplasm between June 2004 and December 2017. They were referred to our hospital for CRS HIPEC. Systemic Chemotherapy regimens were decided by the referring oncologist. We analyze PCI, CC, and use of SC. Overall survival and progression free survival were compared attending to histologic subtype (high- and low-grade adenocarcinomas) and the use of SC.Results: 60 patients were included, 26 were male, median age 63 years (26-81). Median follow-up of 38 months [2-155]. The predominant histologic subtype was mucinous adenocarcinoma (58/60), 1 was colonic type, and 1 adenocarcinoid with signet ring cells. Four patients had extraperitoneal metastases, 2 hepatic metastases (1 with high-grade mucinous adenocarcinoma and 1 with colonic adenocarcinoma), and 2 in the low-grade group developed parenchymal lung disease. Three patients died in the postoperative period. Systemic chemotherapy was administered in 26 patients/57. No difference were observed in the OS and PFS regardless the use of SC in the high- and in the lo-grade groups. Conclusions: The use of SC in low-grade mucinous adenocarcinoma subtype is not supported by our results, and there is no literature date supporting it neither. Palliative SC in high-grade patients deserves of clinical trials for been accepted as standard of care, when benefits are not clearly established by evidence and toxicities are not negligible.

QUIMIOTERAPIA SISTÉMICA EN ADENOCARCINOMAS APENDICULARES CON METÁSTASIS PERITONEALES. ¿VALE LA PENA?

Introduction The role of systemic chemotherapy (SC) in the management of metastatic appendiceal adenocarcinomas is not defined. Methods We perform an observational study of patients treated of peritoneal metastases from appendiceal neoplasm between June 2004 and December 2017. They were referred to our hospital for CRS HIPEC. Systemic Chemotherapy regimens were decided by the referring oncologist. We analyze PCI, CC, and use of SC. Overall survival and progression free survival were compared attending to histologic subtype (high- and low-grade adenocarcinomas) and the use of SC. Results 60 patients were included, 26 were male, median age 63 years (26-81). Median follow-up of 38 months [2-155]. The predominant histologic subtype was mucinous adenocarcinoma (58/60), 1 was colonic type, and 1 adenocarcinoid with signet ring cells. Four patients had extraperitoneal metastases, 2 hepatic metastases (1 with high-grade mucinous adenocarcinoma and 1 with colonic adenocarcinoma), and 2 in the low-grade group developed parenchymal lung disease. Three patients died in the postoperative period. Systemic chemotherapy was administered in 26 patients/57. No difference were observed in the OS and PFS regardless the use of SC in the high- and in the lo-grade groups. Conclusions The use of SC in low-grade mucinous adenocarcinoma subtype is not supported by our results, and there is no literature date supporting it neither. Palliative SC in high-grade patients deserves of clinical trials for been accepted as standard of care, when benefits are not clearly established by evidence and toxicities are not negligible.

Molecular Targeted Therapy in the Management of Recurrent and Metastatic Nasopharyngeal Carcinoma: A Comprehensive Literature Review.

Nasopharyngeal carcinoma (NPC) is the most frequent malignancy arising in the nasopharynx. NPC, to a larger degree, substantially differs from the other malignancies of the head and neck, in terms of incidence, etiology, risk factors, molecular pathogenesis, clinical behavior, management and prognosis. Fundamentally, the management of NPC is entirely guided by the disease stage. Favorably, patients with early- stage disease have encouraging survival outcomes with stand-alone radiation therapy (RT), specifically following the emergence of intensity-modulated RT (IMRT). The reported five-year local control rates are outstanding, and they range from 70% to 90%. Unfortunately, around one-third (30%) of patients presents with loco-regional or distant recurrences, despite rigorous curative treatment in the intermediate (stage II) and advanced (stage III-IVB) NPC disease. At the present time, the management of recurrent and metastatic NPC is largely discouraging and presents significant challenges to the treating physicians. Broadly speaking, there are three management schemes utilized in the management of recurrent and metastatic NPC, namely: (i) palliative systemic chemotherapy, (ii) molecular targeted therapy, and (iii) immunotherapy. The goal of this study is to holistically review the existing body of literature on the utility and safety of molecular targeted therapy in the management of patients with recurrent and metastatic NPC, with a special focus on vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) targets.

The role of liver surgery in patients with isolated breast cancer liver metastases: a meta-analysis

Background: Management breast cancer liver metastases (BCLM) is currently limited to palliative systemic chemotherapy. For selected patients, however, surgical resection may be associated with superior outcomes. Methods: An online database search of MEDLINE was performed. Key bibliographies were reviewed. Studies comparing outcomes for patients with BCLM after liver resection versus medical management were included. Odds ratios with corresponding 95% confidence intervals (CI) by random fixed effect models of pooled data were calculated. Primary endpoints were 1-year, 3-year and 5-year overall survival (OS). Results: The initial literature review yielded 232 articles. Seven articles met inclusion criteria and 4 were included in the final analysis. A total of 890 patients with BCLM were included in the analysis: 234 (26.3%) underwent liver resection and 656 (73.7%) underwent non-surgical management. Mean age was 48.7 years vs. 53.3 years (resection vs. no resection, respectively, p = 0.354). No statistical difference in hormone receptor status, staging, adjuvant therapy was found between 2 groups. Mean time from breast cancer to BCLM was 38.6 and 37.4 months, respectively (p = 0.941). The median survival time was 54.3 months vs. 21.4 months (resection vs. no resection, respectively, p = 0.023). Resection yielded superior 1-year (OR 0.09, 95% CI 0.02–0.49, p < 0.001, Fig. 1), 3-year (OR 0.06, 95% CI 0.04–0.10, p < 0.001, Fig. 2), and 5-year (OR 0.20, 95% CI 0.14–0.28, p = 0.005, Fig. 3) OS when compared to medical management. Conclusion: This is the first meta-analysis assessing the outcomes for patients with BCLM who underwent surgical liver resection. Resection is associated with superior outcomes and should be considered in selected patients with isolated BCLM.

Circulating Biomarkers for Prediction of Objective Response to Chemotherapy in Pancreatic Cancer Patients.

Pancreatic cancer is a lethal disease with increasing incidence. Most patients present with advanced disease, for which palliative systemic chemotherapy is the only therapeutic option. Despite improved median survival rates with FOLFIRINOX or gemcitabine chemotherapy compared to the best supportive care, many individual patients may not benefit from chemotherapy. Biomarkers are needed to predict who will benefit from chemotherapy and to monitor a patient’s response to chemotherapy. This review summarizes current research and future perspectives on circulating biomarkers for systemic chemotherapy response.

An initial experience with Partial ALPPS vs palliative chemotherapy in advanced colorectal liver metastases

Background: Associating liver partition and portal vein ligation (ALPPS) is a novel 2-stage accelerated procedure to treat bilobar colorectal liver metastases with a curative intent. Partial ALPPS (p-ALPPS) is a modified technique whereby 50-80% liver is transected during stage 1. Data comparing survival outcome of p-ALPPS with palliative treatment is still limited. We aim to compare long-term survival of patients who underwent p-ALPPS with patients who received either palliative chemotherapy or best supportive care (BSC). Methods: We retrospectively reviewed 409 patients in our institution with colorectal liver metastases from January 2014 to December 2016. Patients with advanced colorectal liver metastases as defined by >6 metastases and/or > 6 involved segments were identified. These were grouped into 3 main categories: p-ALPPS, palliative chemotherapy and BSC. The median survival in each arm is calculated and compared. Results: 48 patients had advanced bilobar disease. 4 underwent p-ALPPs, 28 received palliative chemotherapy and 16 had BSC. In the p-ALPPS group, 3 have survived more than 365 days (range 366-457) and are still alive. However, 1 demised at 85 days due to chemotherapy related sepsis. Median survival for palliative chemotherapy and BSC are 315 and 97 days respectively. Conclusion: Early data suggests there is a role for p-ALPPS and palliative systemic chemotherapy compared to BSC alone. A more robust study of p-ALPPS outcomes is needed to draw meaningful comparison with palliative chemotherapy.

Personalized cancer medicine : Biomarkers for molecular therapy stratification in pancreatic carcinoma

Ductal adenocarcinoma of the pancreas has avery poor prognosis and arising incidence. Even after curative intent resection, which is possible in aminority of patients, most patients relapse, whereas the majority is diagnosed with inoperable or metastatic disease. That's why palliative systemic chemotherapy is the current therapeutic mainstay. Biomarker-based tumor characterization could identify potential therapy targets and enable apersonalized cancer medicine. Although potentially targetable alterations occur at very low frequencies, the possible impact on patient outcome can be significant. This article summarizes some of the contributions to these aspects and gives an outlook on their clinical meaning.

Randomized control trial comparing quality of life of patients with end-stage peritoneal metastasis treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC) and intravenous chemotherapy.

BackgroundPeritoneal metastasis (PM) is a common occurrence in gynaecological and gastrointestinal cancers and is associated with poor survival. Patients typically present with ascites, abdominal pain, malnutrition, nausea, emesis, and bowel obstruction which significantly compromise the quality of life (QoL). The treatment remains a particular challenge, with palliative systemic chemotherapy being the standard of care. However, the efficacy of systemic chemotherapy is poor but with high potential for side effects and complications. QoL plays an important role in patients with PM and is deteriorating continuously until death. Thus, there is an obvious medical need for better therapeutic options in PM for prolonging survival and preserving QoL by reducing both disease-related symptoms and therapy side effects. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique for delivering pressurized normothermic chemotherapy into the abdominal cavity as an aerosol. This concept seems to enhance the effectiveness of intraperitoneal chemotherapy by taking advantage of the physical properties of gas and pressure by generating an artificial pressure gradient and enhancing tissue uptake and distributing drugs homogeneously within the closed and expanded peritoneal cavity.MethodsThe primary objective of this study is to assess QoL and symptoms in a consecutive cohort of patients with PM treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. QoL is assessed prospectively using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30(Version 3.0) questionnaire. QLQ-C30 is a 30-question self-administered questionnaire inquiring about global health status, 9 individual symptoms, and 5 functional scales. Baseline QoL is measured using the global physical health functional score, and symptom scores derived from EORTC QLQ30 questionnaire before starting therapy, followed by at 60, 120, and 180 days after the first intervention. Calculated sample size is 119 and rounded to 120. For each treatment group, sample size of 60 will be enrolled; Intervention model: IV chemotherapy group (control group) and PIPAC group (experimental group); Study type: prospective randomized control intervention trialDiscussionAll consecutive patients diagnosed with advanced end-stage PM are randomized to be treated with PIPAC or IV chemotherapy. The primary objective of this study is to determine the QoL after three cycles of PIPAC in comparison with six cycles of systemic chemotherapy. The secondary outcome measures include morbidity and mortality. Analysis is by intention to treat.ResultsThe effect of systemic chemotherapy remains limited on the peritoneum due to poor vascularization and low penetration. Side effects after systemic chemotherapy for PM are relatively frequent. QoL plays an important role in these patients and is deteriorating continuously due to the disease or therapy related. Thus, there is need for better therapeutic options for prolonging survival and preserving QoL by reducing both disease-related symptoms and therapy side effects. PIPAC is a novel minimally invasive repeatable treatment modality which demonstrated potentially encouraging tumour response and only minimal toxicity in patients with PM of various origins. It can optimize local drug delivery and improve clinical outcome due to superior pharmacological properties as compared to systemic chemotherapy.Trial registrationREF/2018/08/021225 Registered on Clinical Trials Registry-India (CTRI); www.ctri.nic.in

PIPAC-OV3: A multicenter, open-label, randomized, two-arm phase III trial of the effect on progression-free survival of cisplatin and doxorubicin as Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) vs. chemotherapy alone in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.

BackgroundRecurrent, platin-resistant ovarian cancer (rPROC) has a poor survival. Even with the AURELIA trial, which is the best available treatment today, progression-free survival (PFS) is still only 6.7 months from the start of the second-line chemotherapy. Innovative, effective therapies are urgently needed. Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for administering drugs into the abdomen. PIPAC with cisplatin and doxorubicin (PIPAC C/D) may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low. In a phase II trial with 53 women, 62 % patients had an objective tumor response. Tumor regression on histology was observed in 76 % patients who underwent all three PIPACs. Randomized phase III studies are now required to evaluate the effect of PIPAC C/D compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy).MethodsThe present phase III study is a prospective, open, randomized, multicentric pivotal trial. A total of 244 patients will be randomly assigned (1:1) to the control (A) or to the experimental (B) group. Group A: Systemic palliative chemotherapy, physician’s best choice (monotherapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly. Bevacizumab can be used in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin). Group B: Intraperitoneal chemotherapy, 3×PIPAC C/D, performed every 6 weeks. Combination with systemic therapy is not allowed. Treatment is continued until disease progression, death, or patient refusal. In case of progression, no recommendation for further therapy is given by protocol. Patients are allowed to receive PIPAC C/D or systemic chemotherapy after study termination. The primary endpoint is PFS (according to RECIST v1.1) or death from any cause. The co-primary endpoint is the health-related quality of life (HRQoL) measured as the global health status (GHS, QLQ-30 of EORTC). Secondary outcomes comprise overall survival, safety (CTCAE 5.0), and tumor response according to peritoneal regression grading score (PRGS).DiscussionWe expect PIPAC C/D to control peritoneal disease and preserve the QoL on this subset of patients.Trial registrationThe EudraCT number 2018-003664-31