Liquid Biopsy for Detection of Pancreaticobiliary Cancers by Functional Enrichment and Immunofluorescent Profiling of Circulating Tumor Cells and Their Clusters.

Circulating tumor cells (CTCs) have historically been used for prognostication in oncology. We evaluate the performance of liquid biopsy CTC assay as a diagnostic tool in suspected pancreaticobiliary cancers (PBC). The assay utilizes functional enrichment of CTCs followed by immunofluorescent profiling of organ-specific markers. The performance of the assay was first evaluated in a multicentric case-control study of blood samples from 360 participants, including 188 PBC cases (pre-biopsy samples) and 172 healthy individuals. A subsequent prospective observational study included pre-biopsy blood samples from 88 individuals with suspicion of PBC and no prior diagnosis of cancer. CTCs were harvested using a unique functional enrichment method and used for immunofluorescent profiling for CA19.9, Maspin, EpCAM, CK, and CD45, blinded to the tissue histopathological diagnosis. TruBlood® malignant or non-malignant predictions were compared with tissue diagnoses to establish sensitivity and specificity. The test had 95.9% overall sensitivity (95% CI: 86.0-99.5%) and 92.3% specificity (95% CI: 79.13% to 98.38%) to differentiate PBC (n = 49) from benign conditions (n = 39). The high accuracy of the CTC-based TruBlood test demonstrates its potential clinical application as a diagnostic tool to assist the effective detection of PBC when tissue sampling is unviable or inconclusive.

Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Accurate prostate cancer detection based on enrichment and characterization of prostate cancer specific circulating tumor cells.

BACKGROUND: The low specificity of serum PSA resulting in the inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. The low sensitivity of serum PSA results in false negatives and can miss high-grade prostate cancers. We describe a non-invasive test for detection of prostate cancer based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD-CTCs) from blood samples followed by their identification by immunostaining for pan-cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl-acyl coenzyme-A racemase (AMACR), epithelial cell adhesion molecule (EpCAM), and common leucocyte antigen (CD45). METHODS: Analytical validation studies were performed to establish the performance characteristics of the test using VCaP prostate cancer cells spiked into healthy donor blood (HDB). The clinical performance characteristics of the test were evaluated in a case-control study with 160 known prostate cancer cases and 800 healthy males, followed by a prospective clinical study of 210 suspected cases of prostate cancer. RESULTS: Analytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study. CONCLUSIONS: The test accurately detects PrAD-CTCs with high sensitivity and specificity irrespective of stage, serum PSA or Gleason score, which translates into low risks of false negatives or overdiagnosis. The high accuracy of the test could offer advantages over PSA based prostate cancer detection.

Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle-income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle-income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

Management of human epidermal growth factor receptor 2-negative metastatic breast cancer: Role of poly adenosine diphosphate (ADP-ribose) polymerase inhibitors.

Human epidermal growth factor receptor 2 (HER2)-negative subset is the most heterogeneous group of metastatic breast cancers (MBCs) as it includes both hormone receptor (HR)-positive and HR-negative breast cancer (or TNBC), which have different therapies and treatment challenges. Though endocrine therapy (ET) remains the treatment backbone in HR-positive HER2-negative cases, about 40% of the patients show intrinsic or acquired resistance to ET due to multiple mechanisms. Combining different therapies such as ET and other targeted therapies with or without chemotherapy fails to give continued benefit, unlike cyclin-dependent kinase (CDK) 4/6 inhibitors that have shown a great benefit. TNBC has conventionally been treated ineffectively with systemic chemotherapy. Recently, poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged for HER2-negative breast cancer (BC) patients, including TNBC. Olaparib and talazoparib have recently been approved in germline BRCA-mutated (gBRCAm) HER2-negative MBC. Additionally, ongoing trials of PARPi in combination with various therapies are expected to provide more and better treatment options for gBRCAm HER2-negative breast cancer.

Knowledge, attitudes, and perception of 398 cancer patients toward participation in clinical trials: A single-center study from New Delhi, India.

BACKGROUND AND OBJECTIVE: Clinical trials are considered to be the gold standard research methodology for evaluating the efficacy and safety of healthcare interventions. MATERIALS AND METHODS: A cross-sectional study was conducted using standardized self-administered questionnaires prepared by the research team and statistician. The questionnaires were offered to cancer patients presented at a tertiary care center. RESULTS: We surveyed 398 cancer patients, 193 (48.5%) males and 205 (51.5%) females with a mean (±standard deviation) 55.39 (±13.59) of age in years. Out of total, only 59 (14.82%) had the prior knowledge of the clinical trial. Forty-three (10.80%) participants were willing to participate in clinical trials. CONCLUSION: Cancer patients had preconceived notions and myths that linger in our society that clinical trial participation will harm them. The researchers/oncologists need to explore the rationale, objectives, and benefits of taking part in clinical trials and make it easy to understand by cancer patients.

Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets.

Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10-16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.