Impact Of Anticancer Treatment Research Articles

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE)

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population.

1574P Mortality of 1,636 COVID-19 cancer patients (pts) and associated prognostic factors

We assessed mortality risk by COVID-19 (C19) infection among treated cancer patients (pts) and the impact of anti-cancer treatment (tx) on mortality. Optum de-identified Electronic Health Record dataset (2021-01-07 release) were used to find cancer pts with a C19 positive (ICD-9/10-CM codes U071/U072 or positive test result) or negative (negative test and no positive test at any time after the first negative result) status on the first test/diagnosis date (ie the “index date”). Pts with <1 year database history, with no tx 0-90 days before index, <18 years old, with implausible death dates, and with index dates outside of 02/2020 - 11/2020 were excluded. C19 positive and negative pts were exact-matched on cancer type, then 1:1 nearest-neighbor matched on propensity scores (variables in table). Missing values were imputed (n = 5), and outcomes were evaluated by multivariable logistic regression, including interaction terms between tx and C19 positivity. We identified 21,060 pts, of whom 1,636 (7.8%) were positive for C19 and 19,424 (92.2%) negative. Among 1,636 matched pairs of positive/negative C19 pts, the odds ratio (OR) of 30-day mortality comparing C19 positive vs negative patients was 2.14 (95% CI: 0.71 – 6.52). Among the strongest predictors of 30-day mortality were age 75+ (OR = 5.42, 95% CI: 2.21 – 13.28), inpatient C19 testing/diagnosis (OR = 4.78, 95% CI: 3.04, 7.53), CCI of 3+ (OR = 2.24, 95% CI: 1.30 – 3.89), and metastatic disease (OR = 1.80, 95% CI 1.21 – 2.68). Anti-cancer therapies do not appear to modulate risk of death due to C19. Beyond 30-day mortality, matched mortality rate ratios (MRRs) suggested increased risk for C19 positive patients (MRR = 1.85, 95% CI: 1.26 – 2.44).Table: 1574PSelectˆ OR and 95% CIs for 30-day mortalityOR95% CI, lower95% CI, upperpAnti-cancer txChemotherapy2.100.984.520.06Hormone0.750.272.090.57Immunotherapy1.560.564.390.39Targeted biologic1.580.495.070.41Targeted small molecule2.000.745.440.16C19 positive2.140.716.520.18Interactions with C19Chemotherapy0.810.312.150.67Immunotherapy0.450.141.520.20Hormone therapy1.580.465.360.46Targeted biologic0.490.131.770.26Targeted nonbiologic1.420.464.390.54ˆ Not shown (statistical significance*): (intercept)*, age*, CCI*, index month*, insurance, metastasis*, obesity, region, setting*, sex, smoking status, years since first cancer diagnosis Open table in a new tab ˆ Not shown (statistical significance*): (intercept)*, age*, CCI*, index month*, insurance, metastasis*, obesity, region, setting*, sex, smoking status, years since first cancer diagnosis C19 showed a trend towards increased 30-day mortality risk (not statistically significant), and increased overall mortality risk. Specific tx did not appear to modulate 30-day mortality due to C19.

Abstract PD12-12: Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial

Abstract Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reported outcome (PRO) measure that quantifies cancer patients’ physical function. Responsiveness, the degree to which a scale can assess clinical deterioration and improvement, is an important measurement characteristic that can be assessed by looking at floor and ceiling effects. A floor effect is defined as a high proportion of study participants reporting the lowest possible score in the variable of interest, while a ceiling effect is the opposite. We characterized floor and ceiling effects of the PF subscale in patients with breast cancer enrolled in commercial clinical trials vs. a community-based trial.Objectives: (1) Determine floor/ceiling effects of the QLQ-C30 PF items and subscale among patients receiving treatment for breast cancer (2) Compare floor/ceiling effects among patients enrolled in randomized clinical trials vs. those treated in a community care trial.Methods: PF data from 5 breast cancer commercial clinical trials submitted to the FDA for review were pooled (Clinical Trial or CT Cohort). A subgroup of breast cancer patients from the Alliance PRO-TECT trial was also analyzed (Community Cohort). Descriptive statistics were used to assess floor/ceiling effects, distributions of PF items, and the summed PF score at baseline and follow-up, for both cohorts. Results: The CT Cohort and Community Cohort consisted of 5,975 and 178 patients, respectively. Most patients in both cohorts were female, over the age of 50, and White. They were from varied treatment settings (adjuvant, 1st line, and 2nd line). 78% of CT patients had a baseline ECOG score of 0 (fully active), vs. only 44% in the Community Cohort. Baseline and follow-up floor effects (i.e. % of patients with the lowest response option - “not at all”) are presented in Table 1. Floor effects were more pronounced in the CT Cohort, with 43 to 94% of CT patients responding “not at all” to items in the PF subscale at baseline vs. 24 to 89% in the Community Cohort. Additionally, smaller proportions of CT patients responded “not at all” at Cycle 3 follow up compared to baseline. Meanwhile, floor effects in the Community Cohort were similar at baseline and month 3 follow up.Ceiling effects (i.e. % of patients with the highest domain response) were also observed in both cohorts. Over 54% of CT patients scored ≥93/100 on the 100-point PF subscale, at baseline. This proportion decreased to 30% at Cycle 3 follow up. On the other hand, 26% of community patients scored ≥93/100 on the PF subscale, at baseline. This proportion increased to 30% at Month 3. Conclusion: We observed high floor/ceiling effects in the PF domain of the QLQ-C30 among patients in commercial clinical trials, more so than in the community. Inclusion of patient advocacy groups in the item selection process may increase the relevancy and sensitivity of the PF domain to the population being studied. Stakeholders in clinical trial and clinical practice settings may consider adding additional high functioning items from the EORTC’s item library, to more accurately determine the impact of anti-cancer treatment on patients’ physical functioning. Table 1: Baseline and Follow Up Floor Effects - % of patients responding “not at all”Clinical Trial CohortCommunity CohortBaselineCycle 3BaselineMonth 3ItemQuestion% (n)% (n)% (n)% (n)1Do you have any trouble doing strenuous activities, like carrying a heavy shopping bag or a suitcase?43% (2,540)27% (573)24% (42)27% (43)2Do you have any trouble taking a long walk?60% (3,554)28% (585)24% (42)30% (47)3Do you have any trouble taking a short walk outside of the house?88% (5,256)68% (1,395)58% (104)64% (101)4Do you need to stay in bed or a chair during the day?73% (4,364)57% (1,181)46% (82)51% (81)5Do you need help with eating?94% (5,599)93% (1,904)89% (159)91% (145) Citation Format: Meena N Murugappan, Bellinda King-Kallimanis, Christina Mangir, Lynn Howie, Vishal Bhatnagar, Julia A Beaver, Ethan Basch, Paul G Kluetz. Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-12.

Uterine irradiation as a determinant of infertility and pregnancy losses in young cancer survivors.

Several concerns exist regarding the impact of anticancer treatments on fertility and pregnancy outcome. The detrimental effects of both chemotherapy and radiotherapy on the ovaries are well reported in the available literature. Fewer data are focused on the importance of a functioning uterus to conceive and carry on a healthy pregnancy. The aim of this paper is to provide a narrative review of the current literature to assess the role of uterine irradiation as a potential determinant of infertility and poor obstetrical outcomes. This review addresses the need for multidisciplinary counselling in order to face the poor reproductive and obstetrical outcomes of women who had uterine radiation, according to the different backgrounds (radiotherapy during adulthood versus childhood; total body irradiation versus pituitary, spinal and/or abdominal-pelvic irradiation).

The Importance of Education regarding the Effects of Anticancer Treatment on Fertility and Ovarian Function in the Female Patients with Breast Cancer.

ObjectivesFemale breast cancer patients generally have limited knowledge regarding issues related to preservation of ovarian function and fertility. The present study aimed to explore the change in the understanding of these issues when female breast cancer patients are educated and counseled about ovarian function and fertility after anticancer treatment.MethodsOne hundred nine young female breast cancer patients completed a questionnaire, which revealed their thoughts and opinions before and after receiving the education about ovarian function and fertility. Their responses were analyzed to determine the impact of the education on their perception and understanding of the aforementioned issues.ResultsThe objective survey had four main themes: planning and desire for children, degree of baseline understanding of the effects of anticancer therapy on fertility and ovarian function, resultant change in cognition after education about cancer treatment and its relationship with fertility, and need for education regarding the types of therapies received and their effects on subsequent ovarian function and fertility before treatment.ConclusionsThe preservation of ovarian function and fertility is an important factor that must be included in the discussion prior to initiation of anticancer therapy. Although the study results do not have high educational effectiveness or a high satisfaction with education, there is a need for information and education regarding the impact of anticancer treatment on preservation of ovarian function and fertility.

Clinical characteristics and treatment propensity in elderly patients aged over 80 years with colorectal cancer.

Background/AimsElderly patients (≥ 80 years) with colorectal cancer (CRC) tend to avoid active treatment at the time of diagnosis despite of recent advances in treatment. The aim of this study was to determine treatment propensity of elderly patients aged ≥ 80 years with CRC in clinical practice and the impact of anticancer treatment on overall survival (OS).MethodsMedical charts of 152 elderly patients (aged ≥ 80 years) diagnosed with CRC between 1998 and 2012 were retrospectively reviewed. Patients’ clinical characteristics, treatment modalities received, and clinical outcome were analyzed.ResultsTheir median age was 82 years (range, 80 to 98). Of 152 patients, 148 were assessable for the extent of the disease. Eighty-two of 98 patients with localized disease and 28 of 50 patients with metastatic disease had received surgery or chemotherapy or both. Surgery was performed in 79 of 98 patients with localized disease and 15 of 50 patients with metastatic disease. Chemotherapy was administered in only 24 of 50 patients with metastatic disease. Patients who received anticancer treatment according to disease extent showed significantly longer OS compared to untreated patients (localized disease, 76.2 months vs. 15.4 months, p = 0.000; metastatic disease, 9.9 months vs. 2.6 months, p = 0.001). Along with anticancer treatment, favorable performance status (PS) was associated with longer OS in multivariate analysis of clinical outcome.ConclusionsElderly patients aged ≥ 80 years with CRC tended to receive less treatment for metastatic disease. Nevertheless, anticancer treatment in patients with favorable PS was effective in prolonging OS regardless of disease extent.

Anti-Müllerian Hormone Is a Marker for Chemotherapy-Induced Testicular Toxicity.

Due to increased numbers of young cancer patients and improved survival, the impact of anticancer treatments on fertility has become a major health concern. Despite mounting research on ovarian toxicity, there is paucity of data regarding reliable biomarkers of testicular toxicity. Our aim was to evaluate anti-Müllerian hormone (AMH) as a marker for chemotherapy-induced testicular toxicity. Serum AMH and a panel of gonadal hormones were measured in male cancer patients at baseline and after chemotherapy. In the preclinical setting, mice were injected with diverse chemotherapies and were killed 1 week or 1, 3, or 6 months later. We evaluated spermatogenesis by AMH as well as qualitative and quantitative sperm parameters. Nineteen patients were enrolled, the median age was 38 years (21-44 y). Serum AMH was correlated with increased FSH and T and decreased inhibin-B in gonadotoxic protocols (cisplatin or busulfan) and remained unchanged in nongonadotoxic protocols (capecitabine). AMH expression had the same pattern in mice serum and testes; it was negatively correlated with testicular/epididymal weight and sperm motility. The increase in testicular AMH expression was also correlated with elevated apoptosis (terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labeling) and reduced proliferation (Ki67, proliferating cell nuclear antigen; all seminiferous tubules cells were analyzed). Severely damaged mice testes demonstrated a marked costaining of AMH and GATA-4, a Sertoli cell marker; staining that resembled the pattern of the Sertoli cell-only condition. Our study indicates that the pattern of serum AMH expression, in combination with other hormones, can delineate testicular damage, as determined in both experimental settings. Future large-scale clinical studies are warranted to further define the role of AMH as a biomarker for testicular toxicity.

Anti Müllerian hormone (AMH) as a marker for chemotherapy-induced testicular toxicity: From the bench to the bedside.

e20624 Background: Due to increased numbers of young cancer patients, the impact of anti-cancer treatments on fertility has become a major public health concern. Despite mounting research on ovarian toxicity, there is paucity of data regarding reliable biomarkers of testicular toxicity. We aimed to characterize the role of AMH as a marker for chemotherapy-induced testicular toxicity in both preclinical and clinical settings. Methods: Male patients ( < 45y) who were candidate for chemotherapy were enrolled into the study. Serum AMH and a panel of gonadal hormones were measured at baseline and post-treatment. In the preclinical setting, pubertal mice were injected with saline or various classes of chemotherapies and were sacrificed after 1week or 1/3/6 months post treatment. We evaluated compartments of spermatogenesis by AMH (both proteomics and real-time PCR), as well as qualitative and quantitative sperm parameters. Results: Nineteen patients were enrolled, median age was 38y (21-44y).Serum AMH was corre...

Impact of anticancer treatment on recurrent obstruction in covered metallic stents for malignant biliary obstruction

In patients with unresectable malignant biliary obstruction (MBO), anticancer treatment is often administered. The impact of anticancer treatment on recurrent biliary obstruction in covered self-expandable metallic stents (SEMS) has not been fully elucidated. Data on 279 patients enrolled in a multicenter prospective cohort study of two different covered SEMS for distal MBO, WATCH study (141 partially covered WallFlex stents and 138 partially covered Wallstents) were retrospectively analyzed. The rates and causes of recurrent biliary obstruction (stent occlusion or migration) were compared between anticancer treatment group (n = 173) and best supportive care alone (BSC) group (n = 106). Cumulative time and prognostic factors for recurrent biliary obstruction were analyzed, using a proportional hazards model with death without recurrent biliary obstruction as a competing risk. The overall rate (43 vs. 25%, P = 0.002) and the cumulative incidence (16.1 vs. 8.2, 27.9 vs. 18.9 and 44.1 vs. 26.6% at 3, 6 and 12 months, P = 0.030 by Gray's test) of recurrent biliary obstruction were significantly higher in anticancer treatment group compared with BSC group. The multivariate analysis revealed anticancer treatment [subdistribution hazard ratio (SHR) 1.93, P = 0.007) as well as the use of a partially covered WallFlex stent (SHR 0.65, P = 0.049) as prognostic factors. Anticancer treatment was a risk factor for recurrent biliary obstruction in covered SEMS for distal MBO. The superiority of a partially covered WallFlex stent was again confirmed in this competing risk analysis; UMIN-CTR: UMIN000002293.

What lies behind chemotherapy-induced ovarian toxicity?

Seminal advances in anticancer therapy as well as supportive care strategies have led to improved survival rates, posing an emphasis on preserving an optimum quality of life after cancer treatment. This recognition has paved the way to an increasing research of long-term side effects, both clinical and preclinical and to an ongoing design of a supportive care system to evaluate and treat long-term adverse effects of anticancer treatments, including the impact on fertility. As with many adverse effects induced by anticancer treatments, the literature comprised mostly clinical data with regard to chemotherapy-induced gonadotoxicity, while understanding of the biological mechanism is lagging. The impact of anticancer treatments on female fertility depends on the women's age at the time of treatment, the chemotherapy protocol, the duration, and total cumulative dose administered. Several suggested mechanisms that underlie chemotherapy-induced gonadotoxicity have been described. This review illustrates the clinical evidence, as well as its supportive preclinical studies, while proceeding from the 'bedside to the bench work' and provides an insight to what lies behind chemotherapy-induced gonadotoxicity.

Anticancer treatment and cognitive functions in elderly cancer patients: A prospective study

8543 Background: It has been reported that anticancer treatment may alterate cognitive functions in cancer patients but very few prospective studied addressed this issue. Moreover, little is known about the cognitive impact of anticancer treatment in elderly cancer patients. We aimed at investigating the effect on cognitive functions of antiblastic chemotherapy and endocrine therapy in a consecutive series of elderly cancer outpatients. Methods: We evaluated cognitive functions by means of the Cambridge Cognitive Examination (CAMCOG) test and the Mini-Mental Scale Examination (MMSE) at baseline (before anticancer systemic treatment), after 3 months and after 6 months in cancer patients aged more than 65 years. Mood disturbances such as anxiety and depression were also evaluated (Hospital Anxiety and Depression Scale); comprehensive geriatric assessment and blood tests were performed at each evaluation. Results: Sixty patients were enrolled, 15 patients received chemotherapy (group 1), 13 patients received endocrine therapy (group 2) and 32 patients had neither chemotherapy nor endocrine therapy (group 3, control). Fifty-eight (97%) patients had no evidence of disease at the time of assessment. Median age was 71.5, 73 and 71 years in group 1, 2 and 3, respectively. At baseline, median Activities of Daily Living (ADL) score, Instrumental Activity of Daily Living (IADL) score, number of comorbidities and concomitant medications were 6, 8, 5, 1 in group 1, and 6, 8, 3, 2 in group 2, and 6, 8, 4, 2 in group 3, respectively. Median hemoglobin value was 12.9, 12.8, 13.3 g/dl in group 1, 2 and 3 respectively. At baseline, no significant unbalance was evident among groups. There was a statistically significant correlation between ADL or IADL score and CAMCOG total score (Spearman test, rho=0.4, p&lt;0.05). Higher scolarity level was associated with higher CAMCOG total score. No deterioration of CAMCOG score was evident in group 1, 2 and 3 after 3 and 6 months (paired t-test p&gt;.05); the separate analyses for the different items in CAMCOG test did not evidence any deterioration in time in the 3 groups. No worsening was seen in MMSE. Conclusions: Our study showed that anticancer treatment is not associated with rapid cognitive deterioration in elderly cancer patients. No significant financial relationships to disclose.

OP20. Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy : An issue for measuring the impact of anticancer treatments

OP20. Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy : An issue for measuring the impact of anticancer treatments