Systemic Cancer Therapy Research Articles

An AI Model to Predict Acute Hospitalization after Radiation Therapy

<h3>Purpose/Objective(s)</h3> Acute hospitalization during or after cancer treatment negatively impacts quality of care and causes significant patient morbidity. In patients receiving radiation therapy (RT) for any malignancy, we hypothesized that a machine learning approach would enable prediction of hospitalizations during or shortly after RT. <h3>Materials/Methods</h3> We analyzed 35,810 courses of RT provided to treat a cancer diagnosis at a large multisite academic department in a major metropolitan environment (all cancer patients treated with RT between 8/1999—1/2022 regardless of disease site or treatment intent). Approximately 150 clinical/treatment variables were extracted and processed into analytic format by a proprietary oncology analytics platform connected to the Electronic Medical Record System (inpatient and outpatient), Oncology Information System, and PACS. Such variables included past medical history, recent laboratory data, prior systemic cancer therapies, prior RT, recent hospitalization, and RT details. A patient was labeled as having suffered an acute hospitalization if they had an encounter classified as inpatient or emergency during RT or in the 30 days following completion of RT. A machine learning model was trained on a subset (75%) of the data reserved for training (26857 cases). Five-fold cross-validation was used to select model type and hyperparameters, using area under the ROC curve (AUC) to measure performance. The final model was evaluated for accuracy, AUC, precision, recall, and F1 score on an independent test set (25%) excluded from the training process (8953 cases). Model calibration was assessed by visual inspection of calibration plots. An AUC>0.70 was considered clinically valid. <h3>Results</h3> Among the 35,810 courses of RT, the incidence of acute hospitalization was 9.1% (9.2% training set; 9.0% test set). Model performance on the test set is shown in Table 1. Variables deemed to be significant predictors for hospitalization included recent lab values (PT INR, sodium, potassium) recent hospitalization (within 30 days prior to RT start), and patient age <h3>Conclusion</h3> In cancer patients undergoing RT, a machine learning model identified patients at risk of 30-day hospitalization. Predictive analytics may be a key tool to help providers identify high-risk patients and optimize interventions, while improving quality and value of care.

A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer.

Accurate evaluation of the response to neoadjuvant chemotherapy (NAC) provides important information about systemic therapies for breast cancer, which implies pharmacologicalresponse, prognosis, and guide further therapy. Gene profiles overcome the shortcomings of the relatively limited detection indicators of the classical pathological evaluation criteria and the subjectivity of observation, but are complicated and expensive. Therefore, it is essential to develop a more accurate, repeatable, and economical evaluation approach for neoadjuvant chemotherapy responses. We analyzed the transcriptional profiles of chemo-resistant breast cancer cell lines and tumors of chemo-resistant breast cancer patients in the GSE25066 dataset. We preliminarily screened out common significantly differentially expressed genes and constructed a NAC response risk model using LASSO regression and univariate and multivariate analyses. The differences in bioinformatic features of tumor cells, immune characteristics, and prognosis were compared between high and low-risk group. The potential drugs that could reverse chemotherapy resistance in breast cancer were screened by the CMap database. Thirty-six genes were commonly up/down-regulated in both NAC chemo-resistant tumors and cells compared to the sensitive tumors and wild-type cells. Through LASSO regression, we obtained a risk model composed of 12 genes. The risk model divided patients into high and low-risk groups. Univariate and multivariate Cox regression analyses suggested that the risk score is an independent prognostic factor for evaluating NAC response in breast cancer. Tumors in risk groups exhibited significant differences in molecular biological characteristics, tumor-infiltrating lymphocytes, and immunosuppressive molecule expression. Our results suggested that the risk score was also a good prognostic factor for breast cancer. Finally, we screened potential drugs that could reverse chemotherapy resistance in breast cancer. A novel 12 gene-signature could be used to predict NAC response and predict prognosis in breast cancer.

Systemic therapy for early-stage breast cancer: learning from the past to build the future.

The treatment of breast cancer has improved dramatically over the past century, from a strictly surgical approach to a coordinated one, including local and systemic therapies. Systemic therapies for early-stage disease were initially tested against observation or placebo only in adjuvant trials. Subsequent clinical trials focusing on treatment ‘fine-tuning’ had a marked increase in cohort size, duration and costs, leading to a growing interest in the neoadjuvant setting in the past decade. Neoadjuvant trial designs have the advantages of enabling the direct evaluation of treatment effects on tumour diameter and offer unique translational research opportunities through the comparative analysis of tumour biology before, during and after treatment. Current technologies enabling the identification of better predictive biomarkers are shaping the new era of (neo)adjuvant trials. An urgent need exists to reinforce collaboration between the pharmaceutical industry and academia to share data and thus establish large databases of biomarker data coupled with patient outcomes that are easily accessible to the scientific community. In this Review, we summarize the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era and provide critical insights into how neoadjuvant studies are currently designed, discussing the need for better end points and treatment strategies that are more personalized, including in the post-neoadjuvant setting.

Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis.

Simple SummaryThe current standard of care for patients with HER2-positive early breast cancer who have a pathological complete response after neoadjuvant HER2-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. However, it is not clear how long-term outcomes differ by the HER2-targeted regimen received in each setting. To investigate this question, we pooled patient-level data (n = 1763) from neoadjuvant studies of trastuzumab and pertuzumab to evaluate outcomes with respect to single versus dual HER2 targeting in the neoadjuvant and adjuvant settings. Patients treated with dual HER2-targeted therapy in both the neoadjuvant and adjuvant settings had the highest 4-year event-free survival rates, suggesting that this treatment approach may provide the most benefit for patients with HER2-positive early breast cancer.The standard-of-care for patients with pathological complete response (pCR) after neoadjuvant human epidermal growth factor receptor 2 (HER2)-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. Our objective was to evaluate risk of recurrence or death in these patients and determine if outcomes differed by the HER2-targeted regimen received in each setting. We analyzed patient-level data from five randomized trials evaluating trastuzumab, pertuzumab, or both as part of systemic neoadjuvant and adjuvant therapy for HER2-positive early breast cancer, and assessed event-free survival (EFS) in 1763 patients. Patients with pCR had decreased risk of an EFS event versus those with residual disease (unadjusted hazard ratio [HR] = 0.35; 95% confidence interval [CI]: 0.27–0.46). Regardless of pCR status, after adjusting for baseline factors, reduction in EFS event risk was greater in patients administered pertuzumab/trastuzumab in both settings versus those administered only trastuzumab in both settings (HR = 0.36; 95% CI: 0.26–0.49), or pertuzumab/trastuzumab in the neoadjuvant setting and only trastuzumab in the adjuvant setting (HR = 0.67; 95% CI: 0.47–0.96). Patients with pCR had longer EFS than those with residual disease. Patients treated with pertuzumab/trastuzumab in both the neoadjuvant and adjuvant settings had the lowest risk of breast cancer recurrence.

Feasibility and usability of an electronic patient (pt)-reported outcome (ePRO) smartphone application (app) and biosensor for pts with cancer undergoing systemic therapy.

444 Background: Almost half of the nearly 370,000 pts with cancer who receive chemotherapy in the United States each year experience Emergency Department (ED) visits and unplanned inpatient (IP) stays during treatment, largely due to poorly controlled symptoms. Recent studies show that using PROs in oncology practice can improve symptom management and pt outcomes. This study examines the feasibility and usability of a PRO app paired with a biosensor to identify pts at high risk of ED and IP visits during systemic therapy. Methods: ML41539 is an ongoing prospective observational study evaluating the feasibility and usability of a clinic-provided app and smartwatch biosensor for monitoring pts undergoing systemic cancer therapy (ISRCTN25569053). Key inclusion criteria are 18–80 years old, Eastern Cooperative Oncology Group Performance Status 0–2, biopsy-proven solid tumor diagnosis (excluding non-melanoma skin cancer), and scheduled to receive a first dose of intravenous or oral cancer therapy as an initial or new line of therapy. Exclusion criteria include receiving radiation or hormone therapy only, residing in a skilled nursing facility, or participating in another clinical trial. The app collects 15 common treatment-related symptoms (PRO-CTCAE) daily. Usability and satisfaction were assessed with the modified mHealth App Usability Questionnaire (mMAUQ: score 1-7; higher score indicates better app usability and satisfaction) and the modified Quebec User Evaluation of Satisfaction with Assistive Technology (mQUEST 2.0: score 1-5; higher score indicates better sensor satisfaction). We report planned analysis results of the first 32 pts in the vanguard phase of the trial. Pts wore the biosensor and recorded symptoms on the app for 2 weeks. Results: Thirty-two pts from three Washington State community oncology clinics consented to the vanguard phase. One pt was not onboarded; two dropped out before completing the 2-week observation period. The mean age was 60 years; 68% were women. The most common cancer types were breast (41%), colorectal (13%), endometrial (9%), and melanoma (9%). Of the 29 pts, 59% completed all daily ePRO assessments and 55% wore the sensor every day during the 2-week period. The overall adherence rate was 91% (370/406 assessments) for ePRO and 86% (349/406 biosensor days) for the biosensor. The average mMAUQ score was 6.25 (n = 26); the average mQUEST score was 4.02 (n = 25). Conclusions: Pts receiving systemic cancer therapy had relatively high adherence to a daily digital monitoring system that included an ePRO app and biosensor. Participants expressed moderately high usability of the app and satisfaction with the biosensor. The results support the feasibility of monitoring pts with an app and biosensor. Future studies to assess adherence and data completeness for full courses of systemic therapy are needed. Clinical trial information: ISRCTN25569053.

Patient (pt) experience with a smartphone application (app) and biosensor for remote symptom monitoring during systemic cancer therapy: Qualitative findings from initial testing.

443 Background: Up to half of pts with cancer receiving systemic therapy have unplanned emergency department or hospital admission during treatment. ML41539 is a prospective observational study of an app to collect electronic patient-reported outcomes (ePROs) and a wearable biosensor (Samsung Galaxy Watch3) to evaluate the use of a remote monitoring system to improve symptom management and reduce unplanned admissions (ISRCTN25569053). Here, we report the initial feasibility and usability results for the ePRO app and biosensor. Methods: The study includes a vanguard phase (n = 32) to obtain early feedback on pt experience of the app and biosensor. After 2 weeks of continuous biosensor monitoring and daily ePRO reporting, 10 pts participated in semi-structured telephone interviews conducted by trained study staff. Open-ended questions addressed usability and technology-driven facilitators and barriers. Pts were also asked about ease of use and biosensor comfort on a 10-point Likert scale (higher scores reflected better usability and comfort). Transcripts were summarized using a FITTE-adapted framework and coded in ATLAS.ti 22.0.11.0. Coded data were summarized and consolidated into matrices to identify areas for improvement in future study phases. Results: Participants were approached until the target of 10 completed interviews was met. Respondents resembled the overall study population with regards to gender, race, ethnicity, age, and adherence to wearing the sensor and completing daily ePROs. For ease of use, the average rating among participants was 9 for the app (range 8.5-10) and 9.5 for the biosensor (range 7-10). Biosensor comfort was rated 7 on average (range 3-9). The most common words used to describe the app were “easy,” “simple,” and “straightforward.” Sixty percent of pts said that the watch needed to be charged too often and that their experience could be improved by offering more sensor functions and allowing pts to view and track their ePRO responses and biometric data. Sixty percent of pts also supported using these technologies to monitor symptoms during cancer therapy, stating that it was a good idea or useful, especially if it prevented hospitalization or increased communication with their care team. Conclusions: Overall, pts reported positive experiences wearing the sensor and using the ePRO app to report their symptoms during the 2-week observation period. Ease of use was high for both the app and biosensor. A majority reported dissatisfaction with the battery life of the biosensor. Most stated that they would prefer more opportunities to interact directly with the devices and to monitor their own symptoms by viewing collected ePRO and biometric data. Building this type of functionality into the app and sensor for future study phases could help pts engage more with the devices and potentially improve adherence. Clinical trial information: ISRCTN25569053.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer

BackgroundBoth Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values.MethodsPatients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0–1 and 2–3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method.ResultOne hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0–1 group and was 16.13 months in TRG 2–3 group. TRG 2–3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001).ConclusionTRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

A randomized controlled trial of routine financial toxicity screening via electronic patient-reported outcomes (AFT-39).

180 Background: Financial toxicity affects 20% of cancer survivors and is associated with decreased treatment adherence and poor clinical outcomes. No large-scale programs have been implemented to mitigate financial toxicity among patients undergoing cancer treatment. We evaluated the effect of monthly patient-reported financial toxicity screening as part of a larger digital monitoring intervention. Methods: PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomized 1:1 to digital symptom monitoring with patient-reported outcomes (“PRO practices”) or usual care (“control practices”). Digital monitoring consisted of between-visit online or automated telephone patient surveys containing symptom, functioning, and financial toxicity screening questions for up to one year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this analysis was development or worsening of financial difficulties, assessed via the EORTC QLQ-C30 (“Has your physical condition or medical treatment caused you financial difficulties?”), at any time compared to baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. Results: 1,191 patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the intervention developed, or experienced worsening of, financial difficulties, compared to 39.0% of patients treated at control practices (p = 0.01). Patients and nurses interviewed stated that financial toxicity screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. Conclusions: Screening for financial toxicity as part of routine digital patient monitoring with PROs reduces the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy. Clinical trial information: NCT03249090.

Improving the uptake of prehabilitation interventions for older adults prior to cancer treatment using telehealth in the Geriatric Oncology One-Stop Clinic.

55 Background: Prehabilitation in older patients aged ≥ 65 years undergoing cancer surgery and systemic therapy is crucial in reducing treatment complications and improving physical health, psychological well-being, quality of life (QOL) and cancer-related outcomes. However, a majority of older patients (80%) attending our Geriatric Oncology (GO) One-Stop clinic do not receive same day Comprehensive Geriatric Assessment (CGA)-directed Allied Health Interventions (AHI) for prehabilitation during their First Visit (FV). Objectives: The objective of this study is to increase the uptake of same day CGA-directed AHI for prehabilitation from 20% to 60% using telehealth. Methods: Older patients planned for an FV at the GO One-Stop clinic in an academic tertiary center, the National University Cancer Institute, Singapore (NCIS) were recruited. Our workflow was revised so that all FV patients underwent CGA via telehealth prior to the physical visit. Based on the preliminary CGA findings, a multidisciplinary geriatric oncology board planned for prehabilitation interventions which would be performed on the same day as the physical visit. Interim follow-up via telehealth by GO nurses helped to monitor patients for treatment-related toxicities and development of new geriatric syndromes. QOL was assessed during the FV and 3 months later. Results: Two hundred seventy-five patients were recruited from July 2020 to January 2022. 60% (n = 165) received prehabilitation interventions in the One-Stop clinic. The average time spent per visit was shortened from 4 hours to 2.5hours, but completed interventions on same day rose from 1 to 3. The proportion of patients who responded that they benefited from the program on the patient satisfactory survey remained high at 96%. 84.8% were satisfied with the hybrid telehealth model and 80.8% of them reported a maintained or improved QOL after being enrolled into the program. Conclusions: Adoption of telehealth for CGA is a feasible and effective method in improving prehabilitation interventions uptake for GO patients. GO hybrid model of care is a sustainable practice with no additional cost incurred.

TCL-456 Real-World Use of Mogamulizumab among Patients With Mycosis Fungoides and Sézary Syndrome Before and During COVID-19 in the United States.

Per label, mogamulizumab (Moga) is administered on days 1, 8, 15, and 22 of the first 28-day cycle (loading) and on days 1 and 15 of each subsequent cycle (maintenance) for adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after ≥1 prior systemic therapy. During the COVID-19 pandemic, professional organizations suggested dosing intervals for systemic cancer therapies be extended to limit in-person visits. This study examined the real-world use of Moga before and during the COVID-19 pandemic in the United States. Using the Symphony Health Solutions database, adults with ≥1 diagnosis of MF or SS (ICD-10 CM: C84.0x or C84.1x) and ≥1 Moga claim during 10/1/2018-5/6/2021 were identified. Within the MF (no SS diagnosis) and SS (any SS diagnosis) cohorts, patients were divided into 2 subgroups based on their Moga initiation date: 10/1/2018-3/31/2020 (pre COVID-19) and 4/1/2020-5/6/2021 (COVID-19). Patient characteristics and dosing intervals between Moga doses 1-4 (loading) and between subsequent doses (maintenance) were examined. Overall, 154 MF and 204 SS patients initiated Moga during the study period (mean age: 66.8 and 69.2 years; male: 64% and 55%, respectively). In the MF cohort, 98 and 56 patients were in the pre COVID-19 and COVID-19 subgroups. The mean dosing interval was shorter among patients in the COVID-19 subgroup for both the loading (9.1 vs. 13.2 days) and maintenance doses (15.2 vs. 16.1 days). In the SS cohort, 121 and 83 patients were in the pre COVID-19 and COVID-19 subgroups. Mean loading (9.0 vs. 11.1 days) and maintenance (15.0 vs. 16.8 days) dosing intervals were shorter for patients included in the COVID-19 subgroup. For both MF and SS patients, the COVID-19 subgroup had a higher proportion of patients with ≤10 days between loading doses and ≤21 days between maintenance doses compared to the pre COVID-19 subgroup. Among MF and SS patients, dosing intervals for Moga in loading and maintenance were not extended during the 1st year of the COVID-19 pandemic compared to pre COVID-19. There was a trend towards closer concordance with the label during COVID-19.

Activation of cGAS-STING Signal to Inhibit the Proliferation of Bladder Cancer: The Immune Effect of Cisplatin.

Cisplatin is commonly used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer, but its immune-related mechanism is still unclear. Exploration of the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and explored the important function of these immune effects in the bladder cancer microenvironment in a mice tumor model. We found cisplatin induced immune response in bladder cancer by RNA sequencing and validated that cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8+ T cells and dendritic cells in a transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Our findings indicated a cisplatin-related immune effect in bladder cancer, and cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.

Nebenwirkungsmanagement in der Immunonkologie

The previous articles have addressed various indications for systemic therapy of head and neck cancer. Furthermore, useful considerations pertinent to establishing an outpatient treatment facility have been discussed. A very high proportion of immunotherapeutic agents are employed in an outpatient treatment facility, including nivolumab, pembrolizumab, and cemiplimab. Although these agents are far better tolerated than classical chemotherapeutic drugs, they can also cause severe adverse events. How these can be recognized and treated is the subject of the current article.

Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis.

EP08.02-024 Research Efforts in Systemic Therapy of Lung Cancer With Brain Metastasis From 2015-21: A clinicaltrial.gov Registry Analysis

Oncogene directed therapy and immune checkpoint inhibitor therapies (ICI) resulted in a paradigm shift in non-small cell lung carcinoma (NSCLC) management. With improved survival and extra cranial control, increased likelihood of brain metastasis (BM) is reported. Several clinical trials are evaluating targeted therapy or immunotherapy in BM in lung cancer.

163P Development and validation of the prognostic HER2RI assay for predicting recurrence and survival in early HER2-positive breast cancer

HER2-positive accounts for 15-20% of breast cancers. Today the decision to escalate or de-escalate systemic therapy for early HER2-positive breast cancer is based primarily on traditional clinical factors, which are insufficient to reflect the molecular complexity and heterogeneity of HER2-positive breast cancer. Here we describe the development and validation of a new HER2RI assay, a model that combines expression data of 16 genes and clinical features to obtain risk values to predict the prognosis of early HER2-positive breast cancer.

Therapy resistance mechanisms in hematological malignancies.

Hematologic malignancies are model diseases for understanding neoplastic transformation and serve as prototypes for developing effective therapies. Indeed, the concept of systemic cancer therapy originated in hematologic malignancies and has guided the development of chemotherapy, cellular therapies, immunotherapy and modern precision oncology. Despite significant advances in the treatment of leukemias, lymphomas and multiple myelomas, treatment resistance associated with molecular and clinical relapse remains very common. Therapy of relapsed and refractory disease remains extremely difficult, and failure of disease control at this stage remains the leading cause of mortality in patients with hematologic malignancies. In recent years, many efforts have been made to identify the genetic and epigenetic mechanisms that drive the development of hematologic malignancies to the stage of full-blown disease requiring clinical intervention. In contrast, the mechanisms responsible for treatment resistance in hematologic malignancies remain poorly understood. For example, the molecular characteristics of therapy-resistant persisting cells in minimal residual disease (MRD) remain rather elusive. In this mini-review we want to discuss that cellular heterogeneity and plasticity, together with adaptive genetic and epigenetic processes, lead to reduced sensitivity to various treatment regimens such as chemotherapy and pathway inhibitors such as tyrosine kinase inhibitors. However, resistance mechanisms may be conserved across biologically distinct cancer entities. Recent technological advances have made it possible to explore the underlying mechanisms of therapy resistance with unprecedented resolution and depth. These include novel multi-omics technologies with single cell resolution combined with advanced biocomputational approaches, along with artificial intelligence (AI) and sophisticated disease models for functional validation.

Current Status of PSMA-Targeted Radioligand Therapy in the Era of Radiopharmaceutical Therapy Acquiring Marketing Authorization.

Prostate-specific membrane antigen (PSMA) is highly expressed in PCa, which gradually increases in high-grade tumors, metastatic tumors, and tumors nonresponsive to androgen deprivation therapy. PSMA has been a topic of interest during the past decade for both diagnostic and therapeutic targets. Radioligand therapy (RLT) utilizes the delivery of radioactive nuclides to tumors and tumor-associated targets, and it has shown better efficacy with minimal toxicity compared to other systemic cancer therapies. Nuclear medicine has faced a new turning point claiming theranosis as the core of academic identity, since new RLTs have been introduced to clinics through the official new drug development processes for approval from the Food and Drug Administration (FDA) or European Medical Agency. Recently, PSMA targeting RLT was approved by the US FDA in March 2022. This review introduces PSMA RLT focusing on ongoing clinical trials to enhance our understanding of nuclear medicine theranosis and strive for the development of new radiopharmaceuticals.

Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

BackgroundHigher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. MethodsWe analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight. FindingsData were available for 3504 patients. The median weight change at 3 months was −0.54% (IQR −3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06–1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67–2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites. InterpretationPatients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point. FundingThe creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.

The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future.

Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.

The path to becoming a clinical or radiation oncologist in Nigeria.

The number of cancer patients in Nigeria continues to rise; however, global advances in cancer research are making the provision of optimal care possible. Cancer management is globally agreed to be multidisciplinary, with patients now having the right to benefit from progress in systemic cancer therapy and radio-diagnosis by receiving treatment from adequately trained and highly skilled clinical and radiation oncologists. Radiation oncology is part of the three divisions that make up oncology – medical oncology, surgical oncology and radiation oncology. This discipline in recent times has been developed into Clinical Oncology and although both clinical oncologists and medical oncologists continue to deliver non-surgical cancer treatment, only clinical oncologists are qualified to deliver radiotherapy in the management of cancers. Though clinical oncologists continue to provide quality cancer workforce for the country’s increasing number of cancer patients, much is still unknown about this discipline in Nigeria. It is hoped that inspiring radio-oncologists will take note of the information provided by this article as a guide. This paper chronicles the multifarious process involved in training to become a clinical and radiation-oncologist in Nigeria, plus the requirements, as well as pertinent information a budding physician seeking to advance in this highly specialised field requires.