Artificial Intelligence: A New Tool in Oncologist's Armamentarium

Artificial intelligence (AI) has become an essential tool in human life because of its pivotal role in communications, transportation, media, and social networking. Inspired by the complex neuronal network and its functions in human beings, AI, using computer-based algorithms and training, had been explored since the 1950s. To tackle the enormous amount of patients' clinical data, imaging, histopathological data, and the increasing pace of research on new treatments and clinical trials, and ever-changing guidelines for treatment with the advent of novel drugs and evidence, AI is the need of the hour. There are numerous publications and active work on AI's role in the field of oncology. In this review, we discuss the fundamental terminology of AI, its applications in oncology on the whole, and its limitations. There is an inter-relationship between AI, machine learning and, deep learning. The virtual branch of AI deals with machine learning. While the physical branch of AI deals with the delivery of different forms of treatment—surgery, targeted drug delivery, and elderly care. The applications of AI in oncology include cancer screening, diagnosis (clinical, imaging, and histopathological), radiation therapy (image acquisition, tumor and organs at risk segmentation, image registration, planning, and delivery), prediction of treatment outcomes and toxicities, prediction of cancer cell sensitivity to therapeutics and clinical decision-making. A specific area of interest is in the development of effective drug combinations tailored to every patient and tumor with the help of AI. Radiomics, the new kid on the block, deals with the planning and administration of radiotherapy. As with any new invention, AI has its fallacies. The limitations include lack of external validation and proof of generalizability, difficulty in data access for rare diseases, ethical and legal issues, no precise logic behind the prediction, and last but not the least, lack of education and expertise among medical professionals. A collaboration between departments of clinical oncology, bioinformatics, and data sciences can help overcome these problems in the near future.

The Future of Red Cell Transfusion Lies in Cultured Red Cells

Blood is a very important resource for healthcare-based services and there has been a consistently increasing demand for it in most parts of the world. Poor volunteer-based collection system, high-risk of transfusion-transmitted infections, and emergence of new pathogens as evident from the ongoing Coronavirus Disease 2019 (COVID-19) pandemic are potential challenges to the global healthcare systems. It is imperative to explore safe and reliable alternatives to red cell transfusions. Ex vivo culture of red cells (cRBCs) from different sources such as hematopoietic stem cells (HSCs), pluripotent stem cells, and immortalized progenitors (e.g., BELA-2 cells) could revolutionize transfusion medicine. cRBC could be of great diagnostic and therapeutic utility. It may provide a backup in times of acute shortages in patients with rare blood groups, and in cases with multiple antibodies or sickle cell anemia. The CRISP-Cas9 system has been used to develop personalized, multi-compatible RBCs for diagnostic reagents and patients with multiple allo-antibodies. cRBC could be practically feasible for pediatric patients, who require small quantities of red cell transfusions. cRBC produced under good manufacturing practice (GMP) conditions has been reported to survive in human blood circulation for more than 26 days. Recently, a phase I randomized controlled clinical trial called RESTORE was initiated to assess the survival and recovery of cRBCs. However, feasible technological advancement is required to produce enough cRBCs for clinical use. It is crucial to identify sustainable sources for large-scale production of clinically useful cRBCs. Although the potential cost of one unit of cRBC is extrapolated to be around US$ 8000, it is a life-saving product for patients having rare blood groups and is a “ready to use” source of phenotype-matched, homogenous young red cells in emergency situations.

Administration and Toxicity Profile of the Capizzi Interim Maintenance—Retrospective Study from a Tertiary Care Cancer Centre

Introduction The Capizzi-style methotrexate (MTX) is an integral part of acute lymphoblastic leukemia (ALL) treatment. The escalating dose of MTX originally used in the United Kingdom and Children’s Oncology Group protocols along with L-asparaginase has been modified in the Indian Childhood Collaborative Leukemia (ICiCLe) group protocol where L-asparaginase has been omitted. The data regarding the incidence of toxicities and ease of administration on the Capizzi-style interim maintenance is not robust. Objectives We have compiled our experience with administration and toxicity profile in children with intermediate-risk ALL. Materials and Methods A retrospective data collection of all children diagnosed with intermediate-risk ALL as per the ICiCLe risk stratification in the year 2019 was included in the analysis. Each cycle of MTX was started after ensuring an absolute neutrophil count of >750/mm3 and transaminases <2 upper limit of normal. As a unit protocol, pre- and post-MTX hydration was administered in all our children. No urine pH or midcycle biochemical parameter monitoring was done. Statistical analysis was done using Microsoft Excel and SPSS version 24 IBM Corp. in Armonk, New York, United States. Results Forty-six children were included in the study. The median age of children in our study was 6 years (range: 1 year 2 months–12 years). Undernutrition was associated with a significant increase in toxicity (p = 0.02). Fifty-two percent of children had evidence of toxicity, elevated transaminases being the most common. There were recurring symptoms resulting in 53 episodes of toxicities overall. Incidence of toxicity was more in the early cycles (<3). Conclusion The pre- and post-MTX hydration is an effective way to reduce toxicities with the Capizzi-style MTX and this course can be administered with ease on outpatient basis with minimal need for monitoring or admission.

Real-World Outcome of Platinum-Based Chemotherapy in Advanced Breast Cancer (ABC): A Retrospective Study from a Tertiary Cancer Center in India

Introduction There is a paucity of data on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India. Objectives The objectives were to analyze the efficacy and safety of platinum-based chemotherapy in patients with ABC. Materials and Methods This was a retrospective study of 35 patients with ABC who were treated with platinum-based chemotherapy (gemcitabine and carboplatin, [GC]) in a tertiary cancer center in India from August 2015 to November 2019. The inclusion criteria were patients with ABC, who had received palliative chemotherapy with GC. The exclusion criteria were patients who had received less than two cycles of GC and patients who received platinum-based chemotherapy for neuroendocrine carcinoma of the breast. Results The median age was 45 years (range: 28–68 years). All patients were female (97%) except one male (3%). The histology was ductal carcinoma (77%), mixed (17%), and others (6%). Out of the 12 patients tested for breast cancer (BRCA) gene mutation, six patients had a BRCA mutation. Patients with metastatic and locally progressive disease were 91 and 9%, respectively. The median number of prior lines of systemic therapy for metastatic disease was 1 (range: 0–5). The median number of sites of metastasis was 2 (range: 0–5). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2–6). A dose reduction in chemotherapy was done in 74%. The responses among 34 evaluable patients were complete response (11%), partial response (24%), stable disease (41%), and progressive disease (24%). Grade 3 or more hematological and nonhematological toxicities were observed in 69 and 9%, respectively. The median progression-free survival and overall survival were 6 and 8 months, respectively. The 1-year progression-free survival and overall survival were 19 and 34%, respectively. Multivariate analysis showed that patients who had received more than 3 cycles had a better outcome. Conclusion GC was an active and well-tolerated regimen in ABC regardless of the receptor status. Further prospective randomized studies are warranted to assess the optimal regimen in patients with triple-negative breast cancer.

Palatal mucormycosis in neutropenic children: A Case Report with Review of Literature

Palatal involvement in mucormycosis is mostly secondary to rhino-orbito-cerebral disease, but rarely can be a primary disease of the oral mucosa. This report presents two rare cases of the isolated palatal mucormycosis in neutropenic children and highlights some of the peculiar features of the primary palatal disease and management-related issues in children. A 12-year-old child, who had completed the dexamethasone-based induction phase of chemotherapy for Near Early T cell precursor acute lymphoblastic leukemia, and a 9-year-old boy with a Late Isolated Medullary relapse of B cell acute lymphoblastic leukemia, who was to receive salvage induction chemotherapy, developed palatal discoloration without any other major complaints. Both had neutropenia and were on antifungal prophylaxis. In vitro staining of the discolored mucosa suggested mucormycosis, which was confirmed by pathological examination of the debrided tissue. Computed tomography, done before debridement, showed no significant sinonasal disease enabling us to proceed with the transoral approach. With the help of adjuvant antifungal therapy, the infection could be contained in both cases. This report, along with the reviewed literature, shows that limited palatal mucormycosis can be effectively treated by early diagnosis and debridement and appropriate antifungal therapy. Also, the role of antifungal prophylaxis amongst neutropenic patients has been briefly discussed here.

Efficacy of Mobile Phone Technology for Managing Side Effects Associated with Chemotherapy among Cancer Patients: A Systematic Review and Meta-Analysis

Background To establish the evidence related to the efficacy of mobile phone technology for managing side effects of chemotherapy and improved quality of life among patients with cancer. Methods Articles published in peer-reviewed journals were included in this review. Randomized control trials (RCTs) and non-randomized control trials (non-RCTs) consisting of mobile-based interventions (mobile application, smart phone App-based interventions or guidelines to manage side-effects of chemotherapy or mobile health services), and adult cancer patients (aged 18 or above years) as participants who were undergoing chemotherapy and received mobile phone-based interventions as an interventional group versus control/comparator group who were getting routine or usual care were included in this systematic review. Databases such as Scopus, Science Direct, Cochrane library, PubMed, and Google Scholar were systematically searched between 2007 and 2020. Using the Cochrane risk of bias tool, the methodological quality of the included studies was evaluated by two independent authors. Results We included 10 trials, involving 1467 cancer patients and the number of participants ranged from 50 to 457. All trials measured the side effects of chemotherapy as the main outcome and three trials measured the quality of life as the main outcome.Ten trials included for narrative synthesis showed a significant decrease in chemotherapy side effects and considerable improvement in the quality of life in the interventional group than in the comparison group. Meta-analysis of four RCTs containing 803 subjects concluded a significant improvement (p < 0.0001) in the quality of life.A significant improvement in the quality of life was revealed by random effects model (SMD = 0.31, 95% CI: 0.17, −0.46) and a significant difference (Z = 4.37, p < 0.001) was identified between experimental and control groups. Conclusion Current review strengthens the evidence that utilizing mobile-phone based technology has favorable effects on improving the quality of life by minimizing side-effects associated with chemotherapy among cancer patients.

Retrospective Analysis of Bacterial Isolates during Blood Stream Infections in Children with Chemotherapy-induced Febrile Neutropenia: A Single Centre Experience

Introduction The recent advances in cancer treatment have resulted in significant improvement in the outcome of pediatric cancers. However, febrile neutropenia (FN) is the most important cause of mortality and morbidity in pediatric cancer patients and is a crucial limiting factor for the outcome. The greatest threat that we are facing is the emergence of pan drug-resistant (PDR) organisms. Objectives To study bacterial organisms causing bloodstream infections (BSI) during febrile neutropenia episodes, their antibiotic sensitivity pattern, impact on treatment outcome during the intensive phase of chemotherapy, and the association between prior administration of antibiotics and emergence of multidrug-resistant organisms (MDR). Materials and Methods This retrospective study was conducted in patients between the age group of 0 to 18 years who were treated for malignancies in the division of pediatric oncology at a tertiary center from August 2017 to December 2020. Blood cultures were collected under aseptic precautions, and they were processed as per the Clinical and Laboratory Standard Institute Guideline (CLSI) 2017. Results A total of 122/159 (76.7%) patients were diagnosed to have hematological malignancies, and 37/159 (23.3%) patients were found to be suffering from solid tumors. A total of 309 episodes of FN were documented and 386 cultures were sent, out of which 87/386 (22.53%) cultures were positive for bacteria and 2/386 (2.2%) for fungi. Gram-negative isolates were seen in 51/87 (58.62%) cultures and Gram-positive in 36/87 (41.37%) cultures. Burkholderia cepacia and coagulase-negative Staphylococci (CONS) were the commonest found Gram-negative and Gram-positive bacteria, respectively. MDR bacterial strains were seen in 44/87 (50.57%) cultures and PDR strains in 8/87 (9.2%) cultures. Resistance was higher with Klebsiella species and CONS. There were six mortalities during the induction phase of acute leukemia treatment, out of which 4/6 (66.66%) were due to MDR infections, 1/6 (16.6%) due to fungal infection and chemotherapy refractoriness each. Conclusion Proven bacterial infections were determined in 22.53% of febrile neutropenia episodes. Most BSI in patients with febrile neutropenia were caused by Gram-negative bacteria. Indiscriminate use of higher antibiotics before referral led to the emergence of MDR organisms, thus compromising the outcome. Our study emphasizes the fact that antibiotic stewardship is a crucial task to counter MDR bacteremia-related morbidity and mortality in neutropenic children.

Prognostic Significance of Clinical and Post-Neoadjuvant Chemotherapy Associated Histomorphological Parameters in Osteosarcoma: A Retrospective Study from a Tertiary Care Center

Introduction Osteosarcoma is the most prevalent bone cancer in adolescents. Neoadjuvant chemotherapy (NACT) followed by resection is the current modality of treatment for osteosarcoma. Histological evaluation of extent of tumor necrosis on resection is a well-established prognostic indicator in osteosarcoma correlating with survival in most cases. Objectives The main objective of this study was to establish prognostic significance of various clinical and histological parameters post-NACT in osteosarcoma and to compare the integrated prognostic index proposed by Chui et al, with grading of response to NACT by Huvos and Rosen for osteosarcoma. Materials and Methods This is a retrospective study done over a period of four years and includes 47 cases of osteosarcoma treated with NACT. All slides were reviewed and association of various clinical and histological parameters with overall survival was assessed with chi-squared test and Cox-regression analysis. Results Statistical analysis revealed the prognostic significance of age at presentation, anatomic site, primary tumor size, metastatic status, and clinical stage. Histological parameters such as mitosis ≥10/10hpfs, ≥10% residual tumor were significantly associated with poor survival. Tumor necrosis ≥ 90% (excluding areas of hemorrhage, fibrosis and acellular osteoid) was significantly associated with increased survival. An integrated prognostic index formed by combining above parameters gives a better estimate of overall survival compared with residual disease or necrosis alone. Conclusion Integrated prognostic index improves prognostication in patients treated for osteosarcoma.