Active Anticancer Therapy Research Articles

Usage pattern of anticoagulants in oncology patients receiving active anticancer therapies in Europe and Asia.

e23297 Background: Risks and benefits associated with use of anticoagulants (ACs) in cancer patients should be carefully assessed due to an increased risk of both thrombotic recurrences and bleeding events. Vitamin K antagonists (AVK) have been the most used ACs for patients with atrial fibrillation and venous thromboembolism for many years. Low molecular weight heparins (LMWH) and direct oral anticoagulants (DOACs) are preferred over AVK for cancer associated thrombosis. To better define the current scenario for ACs in cancer patients we propose to use market research data to describe treatment patterns in Europe and Asia. Methods: This study was conducted using Oncology Dynamics, an online secondary market research survey collecting anonymized patient data, from a representative panel of physicians. Data for 11,568 drug-treated oncology patients (p) (9,178 Europe p; 2,390 Asia p) with active cancer and anticoagulant therapies, collected between Q3 2021 and Q3 2023, from 5 European (France, Spain, Germany, Italy, & UK) and 3 Asian countries (China, Japan, & S. Korea), were analyzed. Patients with Genitourinary (GU) tumors were 36%, Lung 19%, Gastrointestinal (GI) 18%, Hepatobiliary/pancreas 12%, Gynecologic (Gyn) 12%, and Melanoma and Brain < 5%. Results: 94% p were aged > 50 years and 49% > 70 years. 64% p were male and 36% female. 67% p showed advanced/metastatic stage vs 33% local/locally advanced stage. Globally, DOACs use was 55%, LMWH 35%, and AVK < 10%; DOACs were the preferred ACs in Europe (64% p) and LMWH in Asia (59% p). Prescription of AVKs in Asia population was higher (17% p) compared with Europe (7% p). Difference in use of ACs by tumor type in European countries in favor of DOACs vs LMWH was noticeable in GU (75% p vs 13% p), GI (61% vs 34%) and Melanoma (71% vs 22%). In Asia population, predominance of LMWH vs DOACs was observable in Gyn (86% p vs 5% p), GI (57% vs 24%) and Hepatobiliary/pancreas (56% vs 35%). AVK were administered in 53% of GU Asia p and DOACs in 31%. Overall, bleeding was more frequently associated with AVK (32% p), compared to DOACs (15% p) and LMWH (9% p). Conclusions: This research highlights the differences in ACs prescription in oncology patients between Asia and Europe, with a preference for LMWH in former and DOACs in the latter. DOACs are the most common ACs prescribed overall, while AVK, associated with higher incidence of bleeding, are used in a small population. A more comprehensive analysis of the included variables will be shared.

Abstract 819: Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer

Abstract The objective of our study is to evaluate the feasibility, acceptance, and impact of patient-centered home care (PCHC) on patient reported outcomes (PROs) and health-related quality of life (HQoL) of black men with advanced prostate cancer (CaP). Meeting patients where they are and offering treatment in or closer to their homes reduce psychological distress and increase treatment compliance, especially for disadvantaged patients in rural areas, those on low incomes, with poor access to transport, elderly and people with disabilities. In 2023, Mayo Clinic has developed the Cancer Care Beyond Walls (CCBW) program, a cancer care delivery model that integrates virtual with in facility treatment and provides a package of care to support administration of cancer-directed therapy (chemotherapy, immunotherapy, hormonal therapy) and/or supportive care in the patients’ homes. Our study will assess if patients and families are comfortable with cancer therapy at home, what factors influences their decision, and use this data to inform our understanding of the proportion of the black men with advanced CaP who would be willing to receive and would benefit from this level of care at home. Patients with advanced CaP from our practice requiring active anti-cancer therapy are administered a brief questionnaire regarding preference for location of therapy at the infusion center or in the home, with perceived difficulties and advantages of each approach. A focus group session with prostate cancer survivor advocates is also conducted to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus a hospital setting. In addition, we are conducting an observational study of 20 patients with advanced prostate cancer receiving supportive care/symptom management and/or anti-cancer therapy in the home as part of the Mayo Clinic CCBW Program to assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support, and establish the impact of home cancer treatment administration on patient-reported function and global health/quality of life, patient-reported symptoms, clinical outcomes, and cost of care. Successful completion of the project will deliver data on patient understanding and acceptability of cancer care at home, strategies for overcoming barriers to care for underserved communities, and the foundation from which we discover, translate and apply new knowledge in administering personalized care to vulnerable populations. Citation Format: Roxana S. Dronca, Folakemi Odedina, Che Ngufor, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi. Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 819.

Investigation of ATR Inhibitor VX970 as a Radiosensitizer in Colorectal Cancer Cells

Colorectal cancer (CRC) is the second leading cause of combined cancer-related mortality in males and females in the U.S. Traditional treatment of locally advanced rectal cancer consists of neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Emerging data suggests that higher response rates can be achieved with total neoadjuvant therapy (TNT) where delivery of all chemotherapy and radiation therapy (RT) occurs prior to surgery. In addition, for patients with a complete response to TNT, non-operative management (NOM) can be considered. However, despite the use of TNT, pathologic complete response rates remain below 40% and NOM is only achieved in approximately 50% of rectal cancer patients. A strong need remains for more active anti-cancer therapies in rectal cancer to both reduce pelvic recurrence and facilitate NOM. Here, we tested the hypothesis that inhibition of the ataxia telangiectasia and Rad3-related protein kinase (ATR), a critical regulator of cellular DNA damage response, could increase the sensitivity of CRC to RT. VX970, a highly potent and selective ATR inhibitor, was investigated as a radiosensitizer in SW48 and LoVo CRC cell models. In vitro, IC50 of VX970 was assessed by alamarBlue cytotoxicity assay, while radiosensitivity was revealed by radiation clonogenic assays (0, 2, 4, 6, 8 Gy). ATR activity was determined by p-Chk1 using immunoblotting, and cell cycle distribution was analyzed by propidium iodide flow cytometry. CRC xenografts were generated using both LoVo and SW48 cells injected in the left flanks of athymic nude mice to explore the radiosensitizing effects of VX970 in vivo. Tumors were allowed to grow to 100-150 mm3, and the mice were randomized into multiple groups [vehicle alone, RT alone (10 Gy/5 fractions), VX970 alone, and VX970+RT]. Mouse weights and tumor size were measured three times weekly. Comparison of treatment groups was performed using the log-rank test with P<0.05 considered significant. The IC50 concentrations of VX970 on SW48 and LoVo cells were about 500 and 100 nM, respectively. VX970 at doses of 3 nM did not alter the viability of CRC cells, but significantly sensitized CRC cells to radiotherapy (P<0.05), with DER of 1.43 and 1.59, respectively, in SW48 and LoVo cells. VX970 efficiently attenuated p-Chk1 expression and significantly abrogated radiation induced G2/M cell cycle arrest (P<0.05). In addition, VX970 in combination with radiotherapy significantly prolonged tumor growth delay of CRC xenografts compared to radiation alone (P<0.05), with minimal toxicity observed. Inhibition of the ATR-Chk1 pathway by targeting ATR kinase with VX970 sensitizes CRC to radiotherapy in vitro and in vivo. Our findings support that ATR inhibition by VX970 is a promising new approach to improve the therapeutic ratio of radiotherapy for patients with CRC and warrants further clinical testing.

An oral triple pill-based cocktail effectively controls acute myeloid leukemia with high translation

Acute myeloid leukemia (AML) is a deadly hematological malignancy characterized by oncogenic translational addiction that results in over-proliferation and apoptosis evasion of leukemia cells. Various chemo- and targeted therapies aim to reverse this hallmark, but most show only modest efficacy. Here we report a single oral pill containing a low-dose triple small molecule-based cocktail, a highly active anti-cancer therapy (HAACT) with unique mechanisms that can effectively control AML. The cocktail comprises oncogenic translation inhibitor HHT, drug efflux pump P-gpi ENC and anti-apoptotic protein Bcl-2i VEN. Mechanistically, the cocktail can potently kill both leukemia stem cells (LSC) and bulk leukemic cells via co-targeting oncogenic translation, apoptosis machinery, and drug efflux pump, resulting in deep and durable remissions of AML in diverse model systems. We also identified EphB4/Bcl-xL as the cocktail response biomarkers. Collectively, our studies provide proof that a single pill containing a triple combination cocktail might be a promising avenue for AML therapy.

Long-term outcomes of COVID-19 infection in patients with solid tumors

Objectives: We analyzed the impact of some clinical and disease-specific factors on the longterm outcomes of SARS-CoV-2 infection in patients with solid tumors. Methods: Total of 739 patients with known solid malignancy and infected by SARS-CoV-2 before the beginning of vaccination were examined. Results: Seventy-six cancer patients died from COVID-19 infection-related effects such as mostly pulmonary and cardiovascular system disorders after a median 16-month follow-up (67.1% and 14.5%; respectively). Compared with survivors (n = 468), non-survivors due to COVID-19 infection related effects (n = 76) were more likely to be aged ≥ 65 years and diagnosis with lung cancer (p = 0.01). Also, female patients were at decreased risk of mortality [OR: 0.34 (95% CI: 0.18-0.65)]. Furthermore, patients with tumor stage IV, active/stable/progressive disease and patients receiving active anticancer therapy were at increased risk of mortality (p = 0.01). Conclusions: The patients with aged ≥ 65 years, diagnosed with lung cancer, receiving active anticancer therapy, with active/stable/progressive and advanced cancer stage were at increased risk of mortality from COVID-19 infection in long-term follow-up.

Cancer care during the Covid-19 pandemic from the perspective of patients and their relatives: A qualitative study

ObjectiveThe Covid −19 pandemic has had a major influence on the organization of cancer care. Little is known about how patients with cancer and their relatives experienced this period. This study explored these experiences and levels of distress and resilience of Dutch cancer patients and their family caregivers during the Covid-19 pandemic. MethodsThe qualitative design included in-depth interviews with cancer patients and their family caregivers to explore their experiences. The distress thermometer (NCCN-DT) and resilience questionnaire (CD-RISC2) were used for contextualizing. Data were analyzed by thematic analysis and descriptive statistics. Results40 patients with breast cancer, lung cancer, colorectal cancer, or melanoma who received active systemic anti-cancer therapy, were included with a median age of 60 years[SD11.1]. We also included fourteen family caregivers with a median age of 60 years [SD8.6].Five themes were identified: (1) Living with cancer during Covid-19, (2) Changes in cancer care, (3) Information and support, (4) Safety inside the hospital, and (5) Impact of vaccination. The mean score of NCCN-DT was 2.9[SD2.4] for patients and 4.3[SD2.7] for family caregivers. Mean score of CD-RISC2 was 6.6[SD1.4] for patients and 7.2[SD1] for family caregivers. ConclusionsPatients felt vulnerable during the pandemic and were strict in following the safety precautions. The limited companionship of family caregivers was experienced as the biggest restraint. In general, they felt safe inside the hospital. Vaccination brought some relief. Patients were satisfied with the provided support, but areas were identified which are amenable for redesigning care processes.

COMPASS-CAT versus Khorana risk assessment model for predicting venous thromboembolic events in patients with non-small cell lung cancer on active treatment with chemotherapy and/or immunotherapy, the CK-RAM study.

Cancer patients are at higher risk for venous thromboembolism (VTE). Several risk assessment models (RAM), including the Khorana and COMPASS-CAT, were developed to help predict the occurrence of VTE in cancer patients on active anti-cancer therapy. We aim to study the prevalence and predictors of VTE among patients with non-small cell lung cancer (NSCLC) and compare both RAMs in predicting VTE in patients with NSCLC were retrospectively reviewed. Variables known to increase the risk of VTE were collected and risk of VTE was assessed using both Khorana and COMPASS-CAT RAM. A total of 508 patients (mean age ± SD, 58.4 ± 12.2 years) were enrolled. Most (n = 357, 70.3%) patients had adenocarcinoma, and 333 (65.6%) patients had metastatic disease. VTE were confirmed in 76 (15.0%) patients. Rates were higher among patients with metastatic disease (19.8%, p < 0.001), adenocarcinoma (17.4%, p = 0.01) and those treated with immunotherapy (23.5%, p = 0.014). VTE rates were 21.2%, 14.1% and 13.9% among those with high (n = 66), intermediate (n = 341) and low (n = 101) Khorana risk scores, respectively (p = 0.126). On the other hand, 190 (37.4%) were classified as high risk by the COMPASS-CAT RAM; 52 (27.4%) of them had VTE compared to 24 (7.5%) of the remaining 318 (62.6%) classified as Low/Intermediate risk level, p < 0.001. In conclusion, patients with NSCLC are at high risk for VTE, especially those with adenocarcinoma, metastatic disease and when treated with immunotherapy. Compared to Khorana RAM, COMPASS-CAT RAM was better in identifying more patients in high-risk group, with higher VTE rate.

Impaired immunogenicity after vaccination for SARS-CoV-2 in patients with gastrointestinal cancer: does tumor entity matter?

SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed. A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibodies (NABs) was measured. Four weeks after second vaccination, adequate titers of SARS-CoV-2 anti-spike immunoglobulin G (IgG) [≥282.0 binding antibody units (BAU)/mL] were found in 62.2% of patients under treatment versus 96.3% of patients in follow-up care (P<0.01). Sufficient titers of SARS-CoV-2 surrogate NAB (≥85.0%) were found in 32.7% of patients under treatment versus 70.6% in follow-up care (P<0.01). Titers of SARS-CoV-2 anti-spike IgG were especially low in patients with colorectal cancer (CRC). For SARS-CoV-2 surrogate NAB, patients with hepatocellular carcinoma (HCC) and with pancreaticobiliary cancer showed the lowest titers (P<0.01). SARS-CoV-2 anti-spike IgG and SARS-CoV-2 surrogate NAB were associated with a correlation coefficient of 0.93. Reaching a titer of SARS-CoV-2 anti-spike IgG ≥482.0 BAU/mL, protective levels of SARS-CoV-2 surrogate NAB (≥85.0%) could be assumed. Following booster vaccination, all patients reached effective antibody titers. Patients with active GI cancer showed impaired immunogenicity after second SARS-CoV-2 vaccination which was overcome by booster vaccination. Our findings were tumor-related and pronounced in patients with CRC and HCC. Waning immunity over time and antibody escape phenomena by variant of concern Omicron must be considered in these especially vulnerable patients.

QOL-04. THE EFFECT OF ART THERAPY ON PATIENT AND CAREGIVER QUALITY OF LIFE IN NEWLY DIAGNOSED HIGH GRADE GLIOMA: A PROSPECTIVE PILOT STUDY

Abstract BACKGROUND High grade gliomas (HGGs) are incurable primary brain tumors, with limited survival times. Patients experience a variety of physical, cognitive, psycho-social changes that may negatively impact patient’s quality of life (QOL). Moreover, patient caregivers’ QOL are also often negatively impacted. As such, interventions to improve patient and caregiver QOL are needed. This study aims to evaluate whether art therapy positively impacts QOL among patients with HGG and their caregivers. METHODS This is a planned study with a target of 20 newly diagnosed or early treatment HGG patients and their caregiver matches. Each patient (with the option of one caregiver per patient) will participate in six (6) monthly art therapy sessions with licensed art therapists and structured curriculum. Patient and caregiver QOL will be assessed before, during, and after the six-month study period using validated scales including the HADS, EORTC-QL-C30, and COQL-C. The data will be aggregated following study completion for statistical modeling. DISCUSSION The positive impact of art therapy on QOL has previously been well established in patients with oncologic and neurologic conditions. However, there is a gap in our understanding of the impact of such therapies among patients with primary neuro-oncologic disorders. These patients face uniquely difficult physical, cognitive, and psychosocial challenges as a result of their unique disease process. It would stand to reason that newly diagnosed HGG patients may benefit from early enrolment and participation in these therapies to improve their overall QOL, particularly shortly after diagnosis and during active anti-cancer therapies. CONCLUSION To our knowledge, this is the first study to assess the impact of such intervention in newly diagnosed HGG patients. This pilot study will assess if early intervention with such therapies can lead to significant changes in patients and/or caregiver measurable QOL metrics.

Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.

Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 for patients with breast and gynecological cancer on active anticancer therapy: Results of a prospective observational study.

BackgroundVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective. Nevertheless, immunocompromised participants were excluded from randomized controlled clinical trials. This study evaluates the efficacy and safety of the Pfizer/BioNTech BNT162b2 (BNT162b2) vaccine in patients with breast and gynecological cancer treated with active anticancer therapy versus a control cohort of healthy participants.MethodsImmune responses to the BNT162b2 vaccine in patients with breast cancer (n = 44) or a gynecological malignancy (n = 6) on active anticancer therapy (28 on chemotherapy, mostly anthracycline- or taxane-based, and 22 on target therapy) and in a control cohort of participants without cancer (n = 67) were investigated by SARS-CoV-2 neutralizing antibody titers measured by S1-binding immunoglobulin G (IgG) concentrations assessed using the LIAISON XL tools (DiaSorin S.p.A.). Response was assessed after a second dose of the BNT162b2 vaccine administered before and at least 3 weeks after the vaccine dose.ResultsOverall, 43/50 (86%) patients of the cancer cohort (74% in the breast cancer group and 100% in the gynecological malignancy group) developed IgG antibodies after the second dose of the BNT162b2 vaccine. There were no statistically significant differences in responder rates between patients treated with chemotherapy and those on target therapy. The majority of patients who received chemotherapy with or without target therapy, 21/28 (75%), developed a reliable antibody titer after a vaccine. All seven non-responder patients were undergoing an anthracycline-based regimen. Based on IgG levels (0–400 AU/ml), patients were classified as negative (‘non-responders’), weakly positive, or strongly positive (‘responders’). No delay in cancer therapy schedule or reported side effects were recorded after BNT162b2 vaccine administration. All healthy participants were strongly positive. Responder rates differed significantly between the two study cohorts (p < 0.001).ConclusionsMost patients develop antibody titers after the second immunization. However, given the persistence of non-responders or weak responders, additional immunization booster seems to be required, along with proactive planning in the vaccination schedule, with vaccine administration spaced out over time with respect to chemotherapy.

Influence of the SARS-CoV-2 outbreak on management and prognosis of new lung cancer cases, a retrospective multicentre real-life cohort study

IntroductionThe SARS-CoV-2 pandemic has impacted the care of cancer patients. This study sought to assess the pandemic’s impact on the clinical presentations and outcomes of newly referred patients with lung cancer from the Greater Paris area. MethodsWe retrospectively retrieved the electronic health records and administrative data of 11.4 million patients pertaining to Greater Paris University Hospital (AP-HP). We compared indicators for the 2018–2019 period to those of 2020 in regard to newly referred lung cancer cases. We assessed the initial tumour stage, the delay between the first multidisciplinary tumour board (MTB) and anticancer treatment initiation, and 6-month overall survival (OS) rates depending on the anticancer treatment, including surgery, palliative systemic treatment, and best supportive care (BSC). ResultAmong 6240 patients with lung cancer, 2179 (35%) underwent tumour resection, 2069 (33%) systemic anticancer therapy, 775 (12%) BSC, whereas 1217 (20%) did not receive any treatment. During the first lockdown, the rate of new diagnoses decreased by 32% compared with that recorded in 2018–2019. Initial tumour stage, repartition of patients among treatment categories, and MTB-related delays remained unchanged. The 6-month OS rates of patients diagnosed in 2018–2019 who underwent tumour resection were 98% versus 97% (HR = 1.2; 95% CI: 0.7–2.0) for those diagnosed in 2020; the respective rates for patients who underwent systemic anticancer therapy were 78% versus 79% (HR = 1.0; 95% CI: 0.8–1.2); these rates were 20% versus 13% (HR = 1.3; 95% CI: 1.1–1.6) for those who received BSC. COVID-19 was associated with poorer OS rates (HR = 2.1; 95% CI: 1.6–3.0) for patients who received systemic anticancer therapy. ConclusionsThe SARS-CoV-2 pandemic has not exerted any deleterious impact on 6-month OS of new lung cancer patients that underwent active anticancer therapy in Greater Paris University hospitals.

FORECAST-1: Feasibility of organoid response assessment to define effective treatments for patients with colorectal cancer after failure of standard therapy.

3583 Background: There are limited treatment options for patients with metastatic colorectal cancer (mCRC) who have progressed on standard therapies. A personalised approach to guide treatment selection would maximise efficacy whilst minimising unnecessary toxicity. Patient derived tumour organoids (PDTO) are self-organizing three-dimensional in vitro models cultured from a fresh tumour biopsy. Drug sensitivity testing on PDTO models have the potential to guide personalised treatment in this clinical setting. Methods: FORECAST-1 is a feasibility study, sponsored by the Australian Gastro-Intestinal Trials Group, of PDTO-based drug sensitivity testing for 30 patients with mCRC that have failed ≥two lines of therapy. Established PDTOs underwent drug sensitivity screening including regorafenib, TAS102, oxaliplatin, irinotecan, 5FU, gemcitabine, pemetrexed and temozolomide. Patients underwent treatment at clinician’s discretion, with clinical response correlated with PDTO response. Results: Between September 2020 and December 2021, 30 patients were enrolled in the study with a median age of 59 years (range 36-71). All patients were ECOG 0-1 and eight patients had received prior TAS102 treatment. Fresh tumour biopsies were obtained from liver (N = 17), soft tissue/peritoneal metastases (N = 5), lung (N = 3), lymph node (N = 2), primary colon (N = 1), brain (N = 1) and bone (N = 1). 20/30 (67%) of patients had successful drug sensitivity screening performed at a median PDTO age of 62 days (range 42-128), nine PDTO cultures failed, and one is still undergoing culture. 15/17 (88%) of PDTO cultures obtained from a fresh liver biopsy were successfully cultured to drug sensitivity testing. 14/20 (70%) of PDTOs that underwent drug sensitivity testing identified therapies with intermediate to high likelihood of clinical response, including regorafenib (N = 7), TAS102 (N = 5), gemcitabine (N = 4), oxaliplatin (N = 3), irinotecan (N = 1), 5FU (N = 1) and temozolomide (N = 1). Subsequent anti-cancer treatment received by patients after study enrolment included TAS102 (N = 7), FOLFOX (N = 3), FOLFIRI+EGFR-inhibitor (N = 2), FOLFIRI (N = 2), regorafenib (N = 1), capecitabine (N = 1) and an immunotherapy based clinical trial (N = 2). As of February 2022, 11 patients remain on active anti-cancer therapy and 17 patients have died. Conclusions: Improving therapeutic selection in refractory mCRC patients remains an area of high clinical need. Two-thirds of patients achieved PDTO establishment to allow drug sensitivity testing in a timely manner. Of these further potentially efficacious treatments were able to be successfully identified. Methods to accelerate PDTO culture and drug testing are being pursued to increase the feasibility of a planned prospective study of PDTO sensitivity informing patient management. Clinical trial information: ACTRN12620001353987.

COVID-19 outcomes in patients with cancer and HIV: An analysis of the COVID-19 and Cancer Consortium (CCC19).

e18790 Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available; bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death; however, additional analyses, including multivariable regression, are warranted.

Antibody responses to SARS‐CoV‐2 vaccination in patients with acute myeloid leukaemia and high risk MDS on active anti‐cancer therapies

Encouraging seroconversion rates to SARS-CoV-2 vaccination in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have been reported in large cohort studies1-4; however, the majority of these patients were not receiving active systemic anti-cancer therapy (SACT) and its impact on vaccine responses remains to be fully elucidated. Mori et al.5 report seroconversion rates of 94.7 and 100% respectively in Japanese patients with AML and MDS after two doses of mRNA SARS-CoV-2 vaccine, of which 39% received SACT. We report SARS-CoV-2 antibody responses following vaccination in a UK cohort of AML and HR-MDS patients all receiving, or having recently completed SACT, and stratified by prior SARS-CoV-2 infection. Demographics, SACT history and laboratory parameters were collected from the electronic health records of patients following two doses of SARS-CoV-2 vaccine (BNT162b2 or ChAdOx1nCoV-19) between December 2020 and July 2021. Serological testing was performed using Roche Elecsys anti-SARS-CoV-2 enzyme immunoassays. A total of 39 patients (85% AML, 15% HR-MDS, median age 63 [21–76]), underwent serological testing after receiving two doses of vaccine (Table 1). All were tested for anti-S antibodies after two doses (median 40 days post-dose) and 59% after the first dose (median 39 days). Thirty-three patients (85%) underwent testing for anti-N antibodies, and seven (21% of those tested) had previous SARS-CoV-2 infection. Eleven patients (28%) received intensive chemotherapy, 51% venetoclax-combination therapy (with azacitidine, low-dose cytarabine or gilteritinib) and 21% non-intensive azacitidine. Seropositivity rates and antibody titres increased with consecutive vaccine doses, from 74% in all patients (75% AML, 67% MDS) to 95% (94% AML, 100% MDS), with a median anti-S titre of 5.90 U/ml (IQR 0.58–56.7) after dose one, rising to 333 U/ml (IQR 86.8–1971) post dose two. Significantly higher titres were detected after dose two in AML patients, but not in MDS, though numbers are small (Figure 1B). We report similar seroconversion rates following two doses as seen by Mori et al. (Figure 1A, Table 1), despite all our patients receiving SACT compared to 39% of their cohort; however, we found no difference in anti-S titres between AML and HR-MDS patients receiving SACT after two vaccine doses (333 iu/ml [IQR 105.9–1896] vs. 495.9 iu/ml [IQR 82.15–2320], p = 0.99). These patterns persisted in patients with no prior SARS-CoV-2 infection and negative anti-N serology (Figures 1C,D and S1, Table 1), although seroconversion rates and median anti-S titres were somewhat reduced. Previous SARS-CoV-2 infection was associated with higher titres after two vaccinations (median 2500 U/ml [IQR 141–2500]), consistent with higher post-vaccination antibody titres in healthy individuals with prior natural infection.6, 7 This highlights the importance of measuring antibody titres, as opposed to seropositivity alone, and considering prior SARS-CoV-2 infection to delineate vaccine responses. Mori et al. reported lower antibody titres after two doses in those AML/MDS patients receiving active SACT as treatment or maintenance therapy (the majority received HMA) compared to those receiving non-chemotherapeutic treatments or completed treatment.5 We observed that no significant difference in seropositivity or anti-S titres was seen in AML patients receiving intensive (28%) compared to non-intensive chemotherapy (21%); however, anti-S titres were significantly reduced in venetoclax-based regimens (55% AML patients, 33% HR-MDS, median 158.5 U/ml [IQR 34.85–873], p = 0.04), independent of previous SARS-CoV-2 infection (Figure 1E,F). Reduced serological responses in patients receiving venetoclax have been previously reported in mature B cell neoplasms and myeloma, but not in AML or MDS.3, 8, 9 Further studies to define the impact of SACT regimens on the magnitude/duration of humoral and T cell responses to SARS-CoV-2 vaccination will have clear implications for this vulnerable group and should be priority questions for larger studies. All patients n = 39 AML n = 33 HR-MDS n = 6 Negative baseline n = 26 Positive baseline n = 7 Jenny O'Nions conceived of the study, performed data collection, data analysis, literature search, and manuscript writing and revision; Wei Yee Chan data collection, data analysis, manuscript writing, and revision; Catherine Zhu performed data collection, manuscript review and revision; Elspeth M. Payne conceived of study, manuscript review and revision; Emilie Sanchez data collection, manuscript review and revision; Adele K. Fielding, Asim Khwaja, Rajeev Gupta, manuscript review and revision. We are extremely grateful to all the patients who participated in this study and to the NHS staff that provided their clinical care. E. M. P. is supported by a CRUK Advanced Clinician Scientist Fellowship (grant no. A24873). RG acknowledges funding from Cure Cancer@ UCL. All authors declare no conflicts of interest. Figure S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Systemic Cancer Therapy Does Not Significantly Impact Early Vaccine-Elicited SARS-CoV-2 Immunity in Patients with Solid Tumors.

mRNA vaccines have been shown to be safe and effective in individuals with cancer. It is unclear, however, if systemic anti-cancer therapy impacts the coordinated cellular and humoral immune responses elicited by SARS-CoV-2 mRNA vaccines. To fill this knowledge gap, we assessed SARS-CoV-2 mRNA vaccine-elicited immunity in a cohort of patients with advanced solid tumors either under observation or receiving systemic anti-cancer therapy. This analysis revealed that SARS-CoV-2 mRNA vaccine-elicited cellular and humoral immunity was not significantly different in individuals with cancer receiving systemic anti-cancer therapy relative to individuals under observation. Furthermore, even though some patients exhibited suboptimal antibody titers after vaccination, SARS-CoV-2 specific cellular immune responses were still detected. These data suggest that antibody titers offer an incomplete picture of vaccine-elicited SARS-CoV-2 immunity in cancer patients undergoing active systemic anti-cancer therapy, and that vaccine-elicited cellular immunity exists even in the absence of significant quantities of SARS-CoV-2 specific antibodies.

Effect of active anticancer therapy on serologic response to SARS-CoV-2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma.

ObjectivesTo evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma.MethodsBetween June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor‐binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma.ResultsAntibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune‐related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity.ConclusionsPatients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Clinical profile and mortality of Sars-Cov-2 infection in cancer patients across two pandemic time periods (Feb 2020–Sep 2020; Sep 2020–May 2021) in the Veneto Oncology Network: The ROVID study

IntroductionWe analyzed a cohort of patients with cancer and Sars-Cov-2 infection from the Veneto Oncology Network registry across two pandemic time periods. Materials and methods761 patients with cancer and SARS-CoV-2 infection were included. Results198 patients were diagnosed during the first pandemic time period (TP1; February 2020 September 2020), 494 during TP2 before the vaccination campaign (TP2/pre-vaccination; September 2020-21 February 2021) and 69 in TP2/post-vaccination (22 February 2021-15 May 2021). TP2 vs TP1 patients were younger (p = 0.004), showed more frequently a good performance status (p < 0.001) and <2 comorbidities (p = 0.002), were more likely to be on active anticancer therapy (p = 0.006). Significantly fewer patients in TP2 (3-4%) vs TP1 (22%) had an in-hospital potential source of infection (p < 0.001). TP2 patients were more frequently asymptomatic (p = 0.003). Significantly fewer patients from TP2 were hospitalized (p < 0.001) or admitted to intensive care unit (p = 0.006). All-cause mortality decreased from 30.3% in TP1, to 8.9% and 8.7% in the two TP2 periods (p < 0.001), reflected by a significant reduction in Sars-Cov-2-related mortality (15.2%, 7.5% and 5.8% in the three consecutive time periods, p = 0.004). ConclusionsDifferences in clinical characteristics and features of Sars-Cov-2 infection between TP1 and TP2 reflect the effects of protective measures and increased testing capacity. The lower mortality in TP2 is in line with a less frail population. However, the vast majority of death events in TP2 were related to COVID-19, reinforcing the priority to protect cancer patients.

Detection of SARS-CoV-2 infection prevalence in 860 cancer patients with a combined screening procedure including triage, molecular nasopharyngeal swabs and rapid serological test. A report from the first epidemic wave.

IntroductionEven if now we have available the weapon of vaccination against SARS-CoV-2, the patients with cancer remains a very frail population in which frequently the immunologic response to vaccination may be impaired. In this setting, the SARS-CoV-2 infection screening retains a great value. However, there are still limited data on the feasibility and efficacy of combined screening procedures to assess the prevalence of SARS-CoV-2 infection (including asymptomatic cases) in cancer outpatients undergoing antineoplastic therapy.Patients and resultsFrom May 1, 2020, to June 15, 2020, during the first wave of SARS-CoV-2 pandemic, 860 consecutive patients, undergoing active anticancer therapy, were evaluated and tested for SARS-CoV-2 with a combined screening procedure, including a self-report questionnaire, a molecular nasopharyngeal swab (NPS) and a rapid serological immunoassay (for anti-SARS-CoV-2 IgG/IgM antibodies). The primary endpoint of the study was to estimate the prevalence of SARS-CoV-2 infection (including asymptomatic cases) in consecutive and unselected cancer outpatients by a combined screening modality. A total of 2955 SARS-CoV-2 NPS and 860 serological tests, in 475 patients with hematologic cancers and in 386 with solid tumors, were performed. A total of 112 (13%) patients self-reported symptoms potentially COVID-19 related. In 1/860 cases (< 1%) SARS-CoV-2 NPS was positive and in 14 cases (1.62%) the specific serological test was positive (overall prevalence of SARS-CoV-2 infection 1.62%). Of the 112 cases who declared symptoms potentially COVID-19-related, only 2.7% (3/112) were found SARS-CoV-2 positive.ConclusionsThis is the largest study reporting the feasibility of a combined screening procedure (including triage, NPS and serologic test) to evaluate the prevalence of SARS-CoV-2 infection in cancer patients receiving active therapy, during the first epidemic wave and under the restrictive lockdown measures, in one of the active areas of the SARS-CoV-2 circulation. Lacking specific recommendations for the detection of asymptomatic SARS-CoV-2 cases, a combined diagnostic screening might be more effective to detect the exact prevalence of SARS-CoV-2 in neoplastic patient population. The prevalence can obviously change according to the territorial context, the entity of the restrictive measures adopted and the phase of the epidemic curve. However, its exact and real-time knowledge could be important to balance risks/benefits of oncologic treatments, avoiding (if the prevalence is low) the reduction of dose intensity or the selection of less intensive (but also less effective) anti-cancer therapies.

Oncologic patients\u2019 misconceptions may impede enrollment into clinical trials: a cross-sectional study

BackgroundClinical trials are an essential source for advances in oncologic care, yet the enrollment rate is only 2-4%. Patients' reluctance to participate is an important barrier. This study evaluates patients' level of understanding and attitudes towards clinical trials.MethodsThis cross-sectional study was conducted in the oncology department and day care unit at the oncology division Tel Aviv Sourasky Medical Center, Israel. From January 2015 to September 2016. Two-hundred patients’ currently receiving active anti-cancer therapy at a large tertiary hospital completed an anonymous questionnaire comprised of demographic information, past experience in clinical research and basic knowledge on clinical trials.ResultsThe majority of respondents did not meet the minimum knowledge level criteria. In those who replied they would decline to participate in a clinical trial, concern were related to potential assignment to the placebo arm, provision of informed consent and trust issues with their oncologist. Those with sufficient knowledge were significantly more interested in participating. Patients with past experience in clinical trials had a higher level of academic education, were less religious, had a better understanding of medical research and were inclined to participate in future research.ConclusionsMisperceptions of clinical trials may contribute substantially to the unwillingness to participate in them.