Administration Of Systemic Chemotherapy Research Articles

Abstract LB024: Permeation enhancer is necessary for the optimized PRV131 mediated cisplatin intratumoral delivery

Abstract PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery. Background: Systemic administration of platinum-based chemotherapy often leads to dose-limiting toxicity, affecting quality of life. While intratumoral delivery may reduce or eliminate the systemic toxicities and adverse side effects associated with intravenous cisplatin chemotherapy, this approach is not commonly adopted, in part due to the difficulty to obtain high drug retention in the tumor and control sustained drug release. PRV131 is a highly-concentrated cisplatin polymeric nanoparticle suspension carefully designed for intratumoral administration. The goal of this study was to assess the safety and efficacy of PRV131 as a monotherapy and in combination with a checkpoint inhibitor in a well-established preclinical murine colorectal adenocarcinoma model. Experimental Methods: MC38 cells were inoculated subcutaneously into the flanks of C57BL/6J female mice and allowed to grow to an average size of 100 mm3. Mice were then randomized into 6 groups of n=10: control (saline injection), 100 µg of cisplatin solution, 400 µg of cisplatin solution, 400 µg of PRV131, 400 µg of PRV131 + 200 µg systemic anti-PD1, and 200 µg systemic anti-PD1. A single injection of PRV131 or cisplatin solution was administered directly into the tumor on Day 1. Intraperitoneal anti-PD-1 was administered on Day 1 and Day 10. Mice were then monitored for efficacy (tumor measurements) and safety (overall health, weight loss and mortality). The durability of a single PRV131 injection was also studied. Efficacy and safety were adjudicated at 28 days post treatment and treatment durability assessment extended through 60 days post inoculation. Results: Our data demonstrates that PRV131 400 µg was significantly more effective than cisplatin solution at an equivalent dose. 80% of PRV131 treated mice survived to day 60 post inoculation, and no detectable tumor was found in 60% of PRV131 treated mice 38 days post administration. The safety profile was acceptable, with no mouse lost more than 20% body weight. Notably, efficacy profile of PRV131 monotherapy did not differ substantially from the addition of anti-PD-1 to the treatment, suggesting a high translational relevance of our drug delivery platform. Conclusion: A single intratumoral injection of PRV131 is well-tolerated in C57BL/6J female mice and elicits a durable antitumor response that lasts for over 30 days, laying the groundwork for its incorporation in clinical trial setting. Citation Format: Manijeh Goldberg, Aaron Manzi, Stefanie Cantin, Peter Conway, Jonathan Shikora, Adelaide McFarland, Matt Cayer, Lillyanna Dunn, Courtney Ball, Alexander T. Pearson, Ari J. Rosenberg, Nishant Agrawal, Evgeny Izumchenko. Permeation enhancer is necessary for the optimized PRV131 mediated cisplatin intratumoral delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB024.

Abstract LB440: PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery

Abstract Background: Systemic administration of platinum-based chemotherapy often leads to dose-limiting toxicity, affecting quality of life. While intratumoral delivery may reduce or eliminate the systemic toxicities and adverse side effects associated with intravenous cisplatin chemotherapy, this approach is not commonly adopted, in part due to the difficulty to obtain high drug retention in the tumor and control sustained drug release. PRV131 is a highly-concentrated cisplatin polymeric nanoparticle suspension carefully designed for intratumoral administration. The goal of this study was to assess the safety and efficacy of PRV131 as a monotherapy and in combination with a checkpoint inhibitor in a well-established preclinical murine colorectal adenocarcinoma model. Experimental Methods: MC38 cells were inoculated subcutaneously into the flanks of C57BL/6J female mice and allowed to grow to an average size of 100 mm3. Mice were then randomized into 6 groups of n=10: control (saline injection), 100 µg of cisplatin solution, 400 µg of cisplatin solution, 400 µg of PRV131, 400 µg of PRV131 + 200 µg systemic anti-PD1, and 200 µg systemic anti-PD1. A single injection of PRV131 or cisplatin solution was administered directly into the tumor on Day 1. Intraperitoneal anti-PD-1 was administered on Day 1 and Day 10. Mice were then monitored for efficacy (tumor measurements) and safety (overall health, weight loss and mortality). The durability of a single PRV131 injection was also studied. Efficacy and safety were adjudicated at 28 days post treatment and treatment durability assessment extended through 60 days post inoculation. Results: Our data demonstrates that PRV131 400 µg was significantly more effective than cisplatin solution at an equivalent dose. 80% of PRV131 treated mice survived to day 60 post inoculation, and no detectable tumor was found in 60% of PRV131 treated mice 38 days post administration. The safety profile was acceptable, with no mouse lost more than 20% body weight. Notably, efficacy profile of PRV131 monotherapy did not differ substantially from the addition of anti-PD-1 to the treatment, suggesting a high translational relevance of our drug delivery platform. Conclusion: A single intratumoral injection of PRV131 is well-tolerated in C57BL/6J female mice and elicits a durable antitumor response that lasts for over 30 days, laying the groundwork for its incorporation in clinical trial setting. Citation Format: Manijeh Goldberg, Aaron Manzi, Stefanie Cantin, Peter Conway, Jonathan Shikora, Adelaide McFarland, Matt Cayer, Lillyanna Dunn, Courtney Ball, Alexander T. Pearson, Ari J. Rosenberg, Nishant Agrawal, Evgeny Izumchenko. PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB440.

Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis.

For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. CRD42023478977. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question.

Proximal gastric cancer—time for organ-sparing approach?

IntroductionA steady increase in gastroesophageal junction and proximal gastric cancer (GC) incidence has been observed in the West. Given recent advances in neoadjuvant chemotherapy (NAC), we sought to characterize short- and long-term outcomes of patients with proximal GC who underwent total (TG) versus proximal gastrectomy (PG). MethodsPatients with stage II/III proximal GC who underwent curative intent treatment between 2009 and 2019 were identified using National Cancer Database (NCDB). Multivariable analysis was used to identify oncological outcomes following TG versus PG. ResultsAmong 7,616 patients with GC who underwent surgical resection, PG and TG were performed on 5,246 (68.8%) and 2,370 (31.2%) patients, respectively. Patients who underwent PG were more likely to receive NAC (TG: 52.3% vs. PG: 64.5%)(p<0.001). On pathologic analysis, patients who underwent TG were more likely to have pT4 tumors (TG: 11.7% vs. PG: 3.1%), metastatic lymph nodes (TG: 64.6% vs. PG: 60.4%), and >16 lymph nodes evaluated (TG: 64.1% vs. PG: 53.1%), yet a lower likelihood of negative resection margins (TG: 86.6% vs. PG: 90.0%)(all p<0.001). While gastrectomy procedure type did not impact long-term survival, receipt of NAC was associated with OS among patients who underwent TG (5-year OS, NAC: 43.5% vs. no NAC: 24.6%) and PG (5-year OS, NAC: 43.1% vs. no NAC: 26.7%)(both p<0.001). ConclusionsPG may be an alternative surgical approach to TG in well-selected patients with proximal GC after administration of preoperative systemic chemotherapy.

Клиническое наблюдение развития острого миелоидного лейкоза у женщины на фоне ремиссии острого лимфобластного лейкоза

The article presents a case of T-cell acute lymphoblastic leukemia (T-ALL) in a patient aged 54 years, against which acute myeloid leukemia developed. The main methods of laboratory examination are given. Intensive polychemo-therapy of T-ALL in 50% of cases causes long-term remission in adults. Treatment of acute T-cell lymphoblastic leukemia consists in long-term intensive systemic chemotherapy and intrathecal administration of chemopreparations. However, despite significant achievements in treatment of patients with this pathology, relapse of the disease occurs in 40% of patients and the risk of secondary leukemia development increases.

Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer.

Peritoneal carcinomatosis (PC) is a common outcome of epithelial ovarian carcinoma and is the leading cause of death for these patients. Tumor location, extent, peculiarities of the microenvironment, and the development of drug resistance are the main challenges that need to be addressed to improve therapeutic outcome. The development of new procedures such as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) have enabled locoregional delivery of chemotherapeutics, while the increasingly efficient design and development of advanced drug delivery micro and nanosystems are helping to promote tumor targeting and penetration and to reduce the side effects associated with systemic chemotherapy administration. The possibility of combining drug-loaded carriers with delivery via HIPEC and PIPAC represents a powerful tool to improve treatment efficacy, and this possibility has recently begun to be explored. This review will discuss the latest advances in the treatment of PC derived from ovarian cancer, with a focus on the potential of PIPAC and nanoparticles in terms of their application to develop new therapeutic strategies and future prospects.

Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials.

To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT). A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867). Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50-54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50-54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50-54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06-2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25-2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26-5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes. The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.

Abstract 3599: Molecular characterization of mouse colorectal cancer cell lines with high potential of peritoneal metastasis

Abstract Background: Peritoneal metastasis occurs in approximately 7% of colorectal cancer (CRC) patients and is associated with worse prognosis compared to non-peritoneal metastasis. In CRC patients with peritoneal metastasis, administration of systemic chemotherapy only slightly improves overall survival. Therefore, a better understanding of the biology of peritoneal metastasis and the development of new molecular therapeutics for CRC patients with peritoneal metastasis are urgently needed. Materials and Methods: CT26 mouse CRC cell lines with low metastatic potentials (CT26-N5) and high metastatic potentials to peritoneum (CT26-P6) were established after several rounds of in vivo selection by orthotopic transplantation of CT26 cells into the syngeneic BALB/c mice. Transcriptomic and proteomic analyses were conducted on CT26-N5 and CT26-P6 cells. Results: Orthotopic transplantation of CT26-P6 cells exhibited significantly increased peritoneal metastasis compared to CT26-N5 cells, while growth of primary tumors was not different between these CT26 sublines. In addition, CT26-P6 cells had higher cell migration and invasion potential in vitro than CT26-N5 cells. Integrated analyses of transcriptome and proteome resulted in identification of molecular signatures associated with peritoneal metastasis. An actin-binding protein Advillin, encoded by the Avil gene, was markedly increased at both mRNA and protein levels in CT26-P6 cells compared to CT26-N5 cells. Knockdown of Avil using siRNA or shRNA in CT26-P6 cells significantly reduced cell migration and invasion in vitro and occurrence of peritoneal metastasis in vivo. Gene Set Enrichment Analysis on transcriptome datasets from CT26-P6 cells and CT26-N5 cells identified interferon gamma response as the most significantly enriched pathway in CT26-cells. In addition, Immunoprecipitation coupled with LC-MS/MS identified potential interaction between Avil and a molecule X that regulates epithelial-mesenchymal transition in CRC. Consistent with the findings in mouse CT26 cells, AVIL knockdown in CRC patient-derived cells (PDCs) suppressed cell migration and invasion in vitro. While AVIL expression was induced by interferon gamma in CRC PDCs, JAK inhibitors, Momelotinib and Ruxolitinib, significantly reduced interferon gamma-induced AVIL expression, suggesting regulation of AVIL by interferon gamma. Conclusion: Molecular characterization of mouse colorectal cancer cell lines with different metastatic potential identified AVIL as a potential therapeutic target in CRC patients with peritoneal metastasis. Regulation of AVIL expression by interferon gamma may suggest functional relevance of tumor immune microenvironment in the development of peritoneal metastasis in CRC. Citation Format: Haruki Mori, Hisanori Isomura, Shuang Zhou, Taisuke Kajino, Yuichi Abe, Takashi Kinoshita, Seiji Natsume, Yusuke Sato, Akira Ouchi, Toru Miyake, Waki Hosoda, Koji Komori, Yasuhiro Shimizu, Masaji Tani, Ayumu Taguchi. Molecular characterization of mouse colorectal cancer cell lines with high potential of peritoneal metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3599.

A League of Its Own? Established and Emerging Therapies in Undifferentiated Pleomorphic Sarcoma.

Over the last decade in soft tissue sarcoma (STS) research, the shifting landscape towards more precise subtype classification and the increasing study of novel therapeutic strategies has prompted a need to highlight current knowledge of effective subtype specific therapies. Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), is among the most common subtypes of STS arising in the trunk or extremities of adults. Administration of systemic chemotherapy is the primary management in locally advanced and metastatic UPS. While anthracycline-based chemotherapy continues to be standard of care in this setting, outcomes in locally advanced or metastatic UPS remain poor. Recent studies highlight the unique characteristics of UPS that may contribute to its greater sensitivity to immune checkpoint inhibition (ICI) compared to other STS subtypes. With the promise of benefit from novel therapies, including ICI or ICI plus chemotherapy, for a subset of patients with UPS comes the need to identify biomarkers predictive of response to therapy. Ongoing and future clinical trials should place strong emphasis on correlative biomarker studies to learn more about the unique biology of UPS and to identify patients for whom ICI-based therapy will be effective.

Inhalable Formulations to Treat Non-Small Cell Lung Cancer (NSCLC): Recent Therapies and Developments.

Cancer has been the leading cause of mortalities, with lung cancer contributing 18% to overall deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The primary form of therapy used to treat lung cancer still includes oral and systemic administration of drugs, radiotherapy, or chemotherapy. Some patients have to go through a regime of combination therapy. Despite being the only available form of therapy, their use is limited due to the adverse effects, toxicity, and development of resistance over prolonged use. This led to a shift and progressive evolution into using pulmonary drug delivery systems. Being a non-invasive method of drug-administration and allowing localized delivery of drugs to cancer cells, inhalable drug delivery systems can lead to lower dosing and fewer systemic toxicities over other conventional routes. In this way, we can increase the actual local concentration of the drug in lungs, which will ultimately lead to better antitumor therapy. Nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening, and tracking. Regardless of the advantages, pulmonary delivery is still in the early stages of development and various factors such as pharmacology, immunology, and toxicology should be taken into consideration for the development of suitable inhalable nano-based chemotherapeutic drugs. They face numerous physiological barriers such as lung retention and efficacy, and could also lead to toxicity due to prolonged exposure. Nano-carriers with a sustained drug release mechanism could help in overcoming these challenges. This review article will focus on the various inhalable formulations for targeted drug delivery, including nano-based delivery systems such as lipids, liposome, polymeric and inorganic nanocarriers, micelles, microparticles and nanoaggregates for lung cancer treatment. Various devices used in pulmonary drug delivery loaded on various nano-carriers are also discussed in detail.

Blockade of ALDH in Cisplatin-Resistant Ovarian Cancer Stem Cells In Vitro Synergistically Enhances Chemotherapy-Induced Cell Death.

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related death. The high mortality and morbidity associated with EOC are mostly due to late diagnosis and chemotherapy drug resistance. Currently, the standard first-line chemotherapy regimen is systemic administration of platinum-based chemotherapy combined with a taxane. A major problem besides cisplatin resistance (occurring in nearly one-third of patients) is the greater toxicity of the drug combinations. A synergistic treatment with drug supporting activity could maximize the cytotoxic effects of chemotherapeutic agents on tumor cells while decreasing the dosage of each drug to potentially reduce toxicity. The ALDH-blocking agent Disulfiram (DSF), a clinically approved drug used for alcoholism treatment, has displayed promising anti-cancer activity. We previously described that blocking ALDH activity enhances the induction of apoptosis, especially in ovarian cancer stem cells treated with chemotherapeutic agents. In this study, we further investigated the synergistic effect of DSF in combination with cytotoxic chemotherapeutic drugs. The concentration of each chemotherapeutic agent could be significantly reduced with sustained efficacy on tumor cell apoptosis in cell lines in vitro (Dose-Reduction Index at IC50 from 1 to 50). Moreover, the potential chemo-sensitizing effects of DSF on ALDH-associated cisplatin-resistant ovarian cancer stem cells were also investigated and shown that in contrast to its high resistance to cisplatin, the cisplatin-resistant cells remain very sensitive to DSF-induced cytotoxicity (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 60.4% vs. 20.5%). In combination with DSF and cisplatin, relatively more apoptosis and necrosis were induced in cisplatin-resistant cells than in their parental cells (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 81.5% vs. 50.1%). A transcriptome analysis identified that ALDH was mainly enriched in the cancer-associated fibroblasts and showed that ALDH plays roles in responding to oxidative stress, metabolisms, and energy transition in the ALDH-associated cisplatin-resistant ovarian cancer stem cells. In conclusion, our data demonstrate a key role of ALDH-associated cisplatin-resistant cancer stem cells and identifies DSF as a potential adjuvant for a rational protocol design by computational quantitative assessment in vitro on ovarian cancer cell lines. Our work contributes to resolving the ALDH-associated cisplatin resistance and provides a resource for the development of novel chemotherapeutic regimens.

Preclinical evidence for mitochondrial DNA as a potential blood biomarker for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side effect of several first-line chemotherapeutic agents including paclitaxel, oxaliplatin and bortezomib, for which no predictive marker is currently available. We have previously shown that mitochondrial dysfunction is associated with the development and maintenance of CIPN. The aim of this study was to evaluate the potential use of mitochondrial DNA (mtDNA) levels and complex I enzyme activity as blood biomarkers for CIPN. Real-time qPCR was used to measure mtDNA levels in whole blood collected from chemotherapy- and vehicle-treated rats at three key time-points of pain-like behaviour: prior to pain development, at the peak of mechanical hypersensitivity and at resolution of pain-like behaviour. Systemic oxaliplatin significantly increased mtDNA levels in whole blood prior to pain development. Furthermore, paclitaxel- and bortezomib-treated animals displayed significantly higher levels of mtDNA at the peak of mechanical hypersensitivity. Mitochondrial complex I activity in whole blood was assessed with an ELISA-based Complex I Enzyme Activity Dipstick Assay. Complex I activity was not altered by any of the three chemotherapeutic agents, either prior to or during pain-like behaviour. These data demonstrate that blood levels of mtDNA are altered after systemic administration of chemotherapy. Oxaliplatin, in particular, is associated with higher mtDNA levels before animals show any pain-like behaviour, thus suggesting a potential role for circulating mtDNA levels as non-invasive predictive biomarker for CIPN.

Efficacy of conversion surgery after a single intraperitoneal administration of paclitaxel and systemic chemotherapy for gastric cancer with peritoneal metastasis.

The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM. We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy. Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien-Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5months and 52.6%, 5.2%, and 0%, respectively. Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy.

The Impact of Treatment at Minority-serving Hospitals on Outcomes for Pancreatic Cancer

Introduction: Healthcare for racial minorities is densely concentrated within a small subset of hospitals in the United States. Understanding outcomes at these minority-serving hospitals (MSH) is highly relevant to the study of racial disparities in cancer care. Our aim was to identify the impact of receiving treatment at an MSH on overall survival (OS) and on receipt of definitive treatment for minority patients with pancreatic cancer. Methods: Using the National Cancer Database, we identified all patients diagnosed with non-metastatic biopsy-proven pancreatic adenocarcinoma between 2004-2014. MSH were defined as institutions in the top decile of proportion of Black and Hispanic patients within the cohort. Univariate and multivariate analyses were performed to assess the influence of patient- and hospital-level factors on OS and receipt of definitive treatment for pancreatic cancer. Results: 21,452 Black and Hispanic patients were included. 4,103(19.1%) were treated at MSH. There was no difference in the proportion of patients undergoing resection(p=0.353). On adjusted analysis, there was no difference in OS for patients treated at MSH versus those treated at non-MSH (Hazard Ratio[HR]=0.99, 95%Confidence Interval[CI]:0.95–1.04;p=0.79). Significant factors associated with a decreased likelihood of death were receipt of surgery (HR 0.44, 95%CI:0.42-0.45), administration of systemic chemotherapy (HR 0.90, 95%CI:0.86-0.94), and high income (HR 0.86, 95%CI:0.80-0.92). Conclusions: For Black and Hispanic patients with non-metastatic pancreatic cancer, there was no difference in OS associated with receipt of treatment at MSH, despite differences in patient demographics and hospital characteristics. Further study is required to identify sources and impact of disparities in cancer care.

Surgical treatment of recurrent ovarian cancer: A review

Aim. To analyze the data available in the modern literature on the role of repeated cytoreduction in the complex treatment of relapses ovarian cancer (OC).&#x0D; Materials and methods. Sources were searched in the following systems Clinicaltrials.gov, PubMed, Medline, NCCN, Scopus, Gynecol Oncol, Elibrary. After analyzing the literature review, 31 sources were used, published from January 1989 to December 2020.&#x0D; Results. The main method of treatment relapses of ОС is administration of systemic chemotherapy. The role of surgical treatment has been actively discussed for several decades. According to the available data of retrospective, prospective, randomized trials, performing surgery following chemotherapy had a favorable effect on the long-term results of treatment just in case of achieving complete cytoreduction in comparison with only chemotherapeutic treatment of platinum-sensitive recurrence of ОС. A validated prognostic model helps to perform the selection of suitable patients for surgical treatment, therefore, the correct selection for secondary cytoreduction allows to identify the patients with a high chance of achieving сomplete cytoreduction, which reduces the number of ineffective operations in patients with residual tumors.&#x0D; Conclusion. Complete cytoreduction of all macroscopically detectable recurrent tumor lesions in combination with subsequent systemic chemotherapy leads to an improvement in progression-free survival and life expectancy in a carefully selected group of patients with platinum-sensitive recurrent OC. Secondary cytoreduction in platinum-refractory and platinum-resistant relapses deteriorates the prognosis and doesn't lead to an increase in survival rates. Patient selection is the key point in secondary cytoreductive surgery. The choice of the methodology of selection of patients is in the process of discussion. When planning treatment, all patients with recurrent OC should be discussed at multidisciplinary teams with the participation of specialists in related specialties. Considering a surgical treatment option should be performed it in large centers with extensive experience in the surgical treatment of OC, relapses, performing complex multi-organ resections.

A simple dilute-and-shoot procedure for the determination of platinum in human pleural effusions using HR-CS GF-AAS

BackgroundHigh-resolution continuum source AAS is an emerging technique for the determination of trace elements in clinical analysis. We aimed to develop a method for the direct determination of platinum (Pt) in pleural effusions that could deepen the understanding of the dynamics of intrapleural Pt concentration during cytostatic therapy. Materials and methodsSamples were collected by thoracic drainage from five patients with lung cancer undergoing platinum based chemotherapy. A simple dilute-and-shoot method for Pt determination in the pleural effusions was developed. Ashing of the sample in an oxygen flow in a graphite tube allowed for direct analysis without prior mineralization. The trueness of the method was verified using an independent technique (ICP-MS). As platinum derivatives are only active in its free form (not bound to proteins), Pt in samples was further divided into free and protein-bound forms by means of ultrafiltration. ResultsUsing the proposed method, Pt contents (free and total) were determined in samples collected at different times after the intravenous application of the Pt derivative. The concentration of total Pt reached values of up to 5,000 μg/L and different patterns of its dynamics in intrapleural fluid were observed. ConclusionsThe developed method enables the fast and simple determination of Pt in biological fluids. It may be applied on a large scale to improve the understanding of Pt dynamics during cytostatic therapy, and also to determine the optimal timing of both thoracic drainage and administration of systemic chemotherapy.

Prognostic factors for bone metastases from head and neck squamous cell carcinoma: A case series of 97 patients.

Although bone is the second-most frequent site of distant metastases of head and neck squamous cell carcinoma (HNSCC), variable prognostic factors in patients with bone metastases from HNSCC have not been fully investigated. The aim of the present study was to assess the prognostic factors affecting overall survival (OS) in these patients. The medical records of 97 patients at two institutions who developed bone metastases from HNSCC between January 2010 and December 2020 were retrospectively reviewed. A multivariate analysis using a Cox proportional hazards model was performed to identify potential clinical predictive factors for longer OS. The median OS was 7 months, and the 1- and 2-year OS rates for all patients were 35.4 and 19.2%, respectively. The independent predictive factors for longer OS were single bone metastasis, good performance status and administration of systemic chemotherapy. The median OS with each predictor was 10, 10 and 10.5 months, respectively. In a selected group of patients with these three factors, the OS was 14.5 months. In conclusion, single bone metastasis, a good performance status and systemic chemotherapy were independent predictors of longer OS in patients with HNSCC, but their contributions were limited.

Mini-Review: PDPK1 (3-phosphoinositide dependent protein kinase-1), An Emerging Cancer Stem Cell Target.

Cancer stem cells (CSCs) are subpopulations of tumor cells that possess abilities for self-renewal, differentiation, and tumor initiation. These rare but therapy-recalcitrant cells are assumed to repopulate tumors following administration of systemic chemotherapy driving therapy failure, tumor recurrence, and disease progression. In early clinical trials, anti-CSC therapies have found limited success to-date possibly due to the inherent heterogeneity and plasticity of CSCs and the incomplete characterization of essential CSC targets. Here, we review the role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as an emerging CSC target. While most previous studies have relied on CSC models which are based on lineage and tissue-specific marker profiles to define the relationships between putative target and CSC traits, this review discusses PDPK1 and its role in CSC biology with an emphasis on CSC systems which are based on proposed function like label-retaining cancer cells (LRCCs).

Successful Pre-Operative Local Control of Skin Invasion of Breast Cancer Using a Combination of Systemic Chemotherapy and Mohs Paste

Locally advanced breast cancer (tumor > 5 cm, widespread infiltration of the skin and muscle, or metastases to lymph nodes) is difficult to resect by surgery, and even when it is resectable, there is a high probability of local recurrence and distant metastasis. Therefore, systemic therapy should be administered first. However, as cutaneous infiltration progresses, the patient's quality of life is impaired by pain, bleeding, presence of exudates, and a foul-smelling odor. Treatment with Mohs paste with systemic therapy can control symptoms associated with skin infiltration and can also be expected to decrease tumor volume. Herein, we report a case in which a tumor was resected following Mohs paste and systemic chemotherapy administration, and the skin defect was reconstructed with a latissimus dorsi myocutaneous flap. We also review the literature for previously reported cases of breast cancer involving Mohs paste.

Systemic chemotherapy for primary cutaneous b-cell lymphoma, leg-type: a case report

Primary cutaneous lymphomas are a group of extranodal B-cell non-Hodgkins lymphomas. Primary cutaneous diffuse B-large cell lymphoma, leg-type, is an extremely rare and aggressive variant of primary cutaneous lymphoma. Due to the contradictory nature, poor prognosis, and high frequency of recurrence of this disease, the treatment of patients is multidisciplinary, based on an accurate histological and immunohistochemical classification as well as risk factor assessment. In this report, we present a clinical case of primary cutaneous B-large cell skin lymphoma, leg-type, with a positive response to chemotherapy.&#x0D; Clinical case. A clinical observation of chemotherapy of a patient with primary B-large cell skin lymphoma, leg-type, is presented. The patient underwent 6 R-CHOP chemotherapy courses and achieved an uncertain complete disease remission.&#x0D; Conclusion. The results obtained confirm the limited literature data on the need for timely administration of systemic chemotherapy in the management of this pathology.