RE: Clinician- and facility-level factors associated with chemotherapy dose reductions in stages I-IIIA breast cancer.

Chemotherapy dose reductions are associated with poorer survival. To better understand the role of clinician- and facility-level factors in chemotherapy dosing, we conducted an analysis within a large, real-world cohort of women with stages I-IIIA breast cancer. Our cohort included 8,540 breast cancer patients receiving chemotherapy at Kaiser Permanente Northern California between 2006 and 2019. Patients were treated across 22 facilities by 198 clinicians. We evaluated associations between clinician- and facility-level factors related to dose reductions at the start of chemotherapy (first cycle dose proportion, FCDP, <90%) and throughout treatment (average relative dose intensity, ARDI, <90%). Prevalence ratios (PR) and corresponding 95% confidence intervals (CI) were estimated for the clinician and facility factors in relation to chemotherapy dose reductions. Factors associated with an increased likelihood of dose reduction were increased clinician years since medical school (FCDP < 90%: PR≥30 vs <10 years : 1.78, p-trend = 0.03; ARDI < 90%: PR≥30 vs <10 years : 1.29, p-trend = 0.03) and treatment at less urban facilities (ARDI < 90%: PR<100% vs 100% urban : 1.38, p-trend = 0.002). Factors associated with a decreased likelihood of dose reduction were higher annual clinician volume of stages I-IIIA breast cancer patients (FCDP < 90%: PR≥30 vs ≤15 patients : 0.64, p-trend = 0.03; ARDI < 90%: PR≥30 vs ≤15 patients : 0.76, p-trend = 0.01), higher treatment facility annual volume of stages I-IIIA breast cancer patients (ARDI < 90%: PR≥200 vs <75 patients : 0.85, p-trend = 0.03), and a larger practice size (FCDP < 90%: PR≥10 vs ≤5 oncologists : 0.53, p-trend = 0.02). Clinician- and facility-level factors were associated with chemotherapy dose reductions. Practice-level changes, such as increasing breast cancer patient volumes and practice size, may support optimal dosing practices.

Older women (>65 years) diagnosed with breast cancer may be at risk for chemotherapy dose reductions. We evaluated associations of age at diagnosis with 2 measures of chemotherapy dose reductions: first cycle dose proportion (FCDP) < 90% and average relative dose intensity (ARDI) < 90%. From the Optimal Breast Cancer Chemotherapy Dosing study, we included 10166 women aged 18+ years treated with adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California (KPNC) and Washington (KPWA) between 2004 and 2019. We examined associations between age at diagnosis with FCDP < 90% (reflecting clinician intent at chemotherapy initiation) and ARDI < 90% (reflecting average dose across the chemotherapy course). We used generalized linear models of the Poisson family with a log-link function and robust standard errors to calculate prevalence ratios (PR) for FCDP < 90% and ARDI < 90% with 95% confidence intervals (CI) adjusted for patient and tumor characteristics, with and without adjusting for pre-existing comorbidities. All tests for statistical significance were 2-sided. The proportion of women with FCDP < 90% ranged from 2.9% among women aged 18-39 years to 18.6% among women aged 75+ years. Before adjusting for comorbidities, women aged 75+ years were more likely to have FCDP < 90% (PR = 4.88; 95% CI = 3.58 to 6.66) and ARDI < 90% (PR = 1.91; 95% CI = 1.58 to 2.32) versus women aged 40-49 years. Results were similar after adjusting for comorbidities as a composite comorbidity score or individual comorbidities. Older age at diagnosis was strongly associated with chemotherapy dose reductions in this population-based cohort, particularly at chemotherapy initiation but also across the course of treatment.

Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Patients with Solid Tumors

Effect of Body Mass Index– and Actual Weight–Based Neoadjuvant Chemotherapy Doses on Pathologic Complete Response in Operable Breast Cancer

e18657 Background: Despite adolescent and young adults (AYAs) representing the patient population most likely to initiate and use tobacco and illicit drugs, studies of their impact have thus far focused on older cancer patients or those in survivorship. As sarcomas often serve as a model for AYA care and are associated with poor psychosocial function, frequent delays in diagnosis, and outcomes related to chemotherapy dose density, we sought to understand the impact of tobacco and illicit drug use on diagnosis, chemotherapy delays and dose reductions, and no-show rates in AYAs with sarcoma. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with sarcoma seen at least once in 2019 at the University of Wisconsin, identifying documentation of tobacco, marijuana, and other illicit drug use and comparing to pre-identified cancer outcomes including days from symptom onset to tissue diagnosis (with delay defined as &gt; 120 days from symptoms to diagnosis), chemotherapy delays &gt; 1 week and dose reductions, and appointment no-show rates. Current substance use was defined as use following cancer diagnosis. Results: We identified 46 AYAs with sarcoma, with documented tobacco use in 20% as current (9/46), 13% as former (6/46) and 67% as none (31/46). Marijuana and illicit drug use were less frequent at 17% (8/46) and 7% (3/46) respectively. Delayed diagnoses were more common in patients with current tobacco use (6/9, 67%) as compared with former or non-smokers (12/37, 32%, p = 0.12) and were seen in all patients with illicit drug use (3/3, 100%), as compared with only 35% without illicit drug use (15/43, p = 0.05). Of the 24 patients who received chemotherapy, chemotherapy delays and dose reductions were more common in current tobacco users at 86% (6/7) and 29% (2/7) respectively, as compared with patients with former or no tobacco use at 71% (12/17) and 18% (3/17) respectively. Chemotherapy dose reductions were also more common in patients with illicit drug use (2/3, 67%) versus no illicit drug use (3/21, 14%, p = 0.10). Appointment no-show rates were higher in current tobacco users versus former or non-smokers, with 44% (4/9) versus 27% (10/37) with a no-show rate &gt; 5%. In patients with documented substance use, oncology providers documented 93% of tobacco use (14/15) but only 38% marijuana use (3/8) and 33% illicit drug use (1/3) and no oncology providers documented a cessation plan. Conclusions: Current tobacco and illicit drug use in AYAs with sarcoma were associated with delays in diagnosis, increased chemotherapy delays and dose reductions, and higher no-show rates, highlighting modifiable risk factors. Even more strikingly, oncology providers had low rates of documentation of marijuana and illicit drug use in AYAs and no documentation of plans for cessation, highlighting a lost opportunity and the need for more standardized substance use assessment and evidence-based cessation interventions for AYAs with cancer.

Background: Chemotherapy is widely used to treat early stage breast cancer (ESBC). Dose reductions and dose delays–e.g., due to advanced age or severe/febrile neutropenia–are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of chemotherapy dose reductions and dose delays among women with ESBC in clinical practice. Methods: This study employed a retrospective cohort design and electronic medical records from over 60 community oncology clinics in more than 20 states (2004-2010). Study population included adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidences of chemotherapy dose delays (≥7 days for any drug in ≥1 cycles), chemotherapy dose reductions (≥15% for any drug in ≥1 cycles), and low relative chemotherapy dose intensity (&amp;lt;85% over the course) – relative to physician-reported planned chemotherapy administration – were descriptively analyzed for the seven most frequently observed regimens among subjects. Results: 2,350 women received seven most frequently observed regimens (80% of study population); mean age – across regimens – ranged from 51–56 years, and 31–94% received primary prophylaxis against severe/febrile neutropenia with a colony-stimulating factor. Incidence of dose reductions ranged from 17–48%, and dose delays, from 24–45%. Overall mean relative dose intensity (RDI) ranged from 80%-99%, and 17–50% of subjects received RDI &amp;lt;85%; mean RDI among those with low RDI ranged from 40%-67%. Discussion: Chemotherapy dose delays and dose reductions are common in ESBC, among those receiving dose-dense as well as conventional regimens. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-11.

A Prospective Multivariate Analysis of Risk Factors Associated with Occurrence of Febrile Neutropenia in Any Cycle in NHL Patients Receiving Chemotherapy.

Chemotherapy is widely used to treat early stage breast cancer (ESBC). Reductions and delays in dose administered--e.g., due to advanced age or febrile neutropenia (FN)--are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of reduced chemotherapy dose intensity among women with ESBC in the current era of US clinical practice. This study employed a retrospective cohort design and electronic medical records from > 65 community oncology/hematology clinics in > 35 states (2004-2010). The study population comprised adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidence of chemotherapy dose delays (≥ 7 days for any drug in ≥ 1 cycles), chemotherapy dose reductions (≥ 15% for any drug in ≥ 1 cycles), and low chemotherapy relative dose intensity (RDI <85% over the course) relative to published reference standards were descriptively analyzed for the seven most-frequently planned regimens in the study database. A total of 2,228 women (70% of the subjects who received chemotherapy for ESBC and met other selection criteria) initiated 1 of the 7 most-frequently planned regimens. Mean age of subjects was 54 years and 69% received primary prophylaxis against FN with a colony-stimulating factor. Incidence of dose delays, dose reductions, and low RDI was 31, 24, and 26%, respectively; low RDI typically was due to premature treatment discontinuation. For patients (n = 626) receiving the most common regimen (dose-dense AC-T: doxorubicin/cyclophosphamide, Q2 × 4 cycles, paclitaxel or docetaxel, Q2 × 4 cycles), incidence of dose delays, dose reductions, and low RDI was 42, 29, and 32%, respectively. In the current era of US clinical practice, chemotherapy dose delays and dose reductions are common among women with ESBC receiving frequently used myelosuppressive dose-dense, as well as conventional, chemotherapy regimens.

PCN180 PREDICTORS AND PREVALENCE OF CHEMOTHERAPY DOSE REDUCTION AMONG PATIENTS WITH METASTATIC COLORECTAL CANCER

Background:The benefit of chemotherapy in colon cancer patients is well documented but depends largely on whether patients complete the planned treatment regimen. We evaluated predictors of early discontinuation (EDChemo) and dose reduction of chemotherapy, especially the role of adverse treatment effects, in stage III patients who received adjuvant chemotherapy.Methods:Stage III colon cancer patients who were diagnosed in 2003–2014 and recruited into a population-based study in Germany and received FOLFOX [5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin], capecitabine monotherapy (CapMono), or 5-FU/LV were included. We assessed determinants of EDChemo and dose reduction using multivariable logistic regression. Also, we estimated proportions of EDChemo and dose reduction that are attributable to adverse effects using attributable fractions.Results:EDChemo and dose reduction rates were 52% and 17% for FOLFOX, 28% and 9% for CapMono, and 45% and 6% for 5-FU/LV, respectively. Predictors of EDChemo were low-grade tumor and treatment in a medium-volume hospital (for FOLFOX), obesity (for CapMono), and increasing age, T4 stage, and treatment in a medium-volume hospital (for 5-FU/LV). Adverse effects were particularly strongly associated with EDChemo and contributed to about 63%, 51%, and 32% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Of the various adverse effects, gastrointestinal events showed the strongest associations with EDChemo and accounted for about 7%, 26%, and 20% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Adverse effects were, moreover, a strong determinant of dose reduction and accounted for about 82% of all cases.Conclusions:EDChemo is common in stage III colon cancer patients receiving chemotherapy and more than half of the cases of EDChemo and dose reduction are due to adverse treatment effects. Further research should address the potential for reducing EDChemo and dose reduction rates by close monitoring of patients for early signs and enhanced management of adverse effects, especially gastrointestinal events.

Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

Aim: to conduct a comparative analysis of the safety of postoperative accelerated hypofractionated radiotherapy for patients with stage I-IIIA breast cancer. Material and Methods. From 2013 to 201, 316 patients with stage I-IIIA breast cancer were treated at A.F. Tsyb Medical Radiological Research Center. Postoperative accelerated hypofractionated radiotherapy at a single daily dose of 2.7 Gy to a total dose of 40.5 Gy was given to 223 patients. The control group patients received the conventional radiation therapy at 2 Gy per fraction to a total dose of 50 Gy (n=93). The quality of life of patients was evaluated using the questionnaire EQ-5D consisting of descriptive part and a visual analogue scale (EQ VAS). Results. The frequency of edema of the upper limb did not depend on the fractionation regimen. This complication occurred more often in cases with axillary radiotherapy ( р &lt;0.01) and in cases with radical mastectomy. No difference in the quality of life between the patient groups was found. Conclusion. Postoperative accelerated hypofractionated radiotherapy at 2.7 Gy per fraction to a total dose of 40.5 Gy is safe and can be used after both organ-sparing surgery and radical mastectomy. This radiotherapy regimen is more preferable than the conventional one due to the reduced treatment time. Axillary radiotherapy signifcantly increases the risk of lymphedema of the upper limb.

Dose reduction during concurrent chemoradiotherapy (cCRT) is frequently required in patients with limited-stage small-cell lung cancer (LS-SCLC) because of treatment-related toxicities or poor tolerance. However, the impact of chemotherapy dose reduction on long-term outcomes in LS-SCLC remains unclear. We aimed to evaluate whether chemotherapy dose reduction compromises survival in patients with LS-SCLC receiving definitive cCRT. We retrospectively analyzed patients with LS-SCLC treated with definitive cCRT across multiple centers. Patients were categorized into a dose-maintained group and a dose-reduced group according to whether chemotherapy dose reduction occurred during cCRT. To minimize baseline imbalances, inverse probability of treatment weighting (IPTW) based on propensity scores was applied using clinical covariates including age, sex, T stage, N stage, ECOG performance status, smoking status, weight loss, gross tumor volume, and chemotherapy regimens. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models in both unweighted and IPTW-weighted cohorts. Exploratory analyses were additionally performed within the dose-reduced group according to the timing of first dose reduction and the magnitude of dose reduction. A total of 1,013 patients were included, comprising 627 patients in the dose-maintained group and 386 patients in the dose-reduced group. After IPTW adjustment, baseline characteristics were well balanced between groups. For OS, the median OS after IPTW adjustment was 57.8months (95% CI 42.9-70.1) in the dose-maintained group and 42.8months (95% CI 37.5-67.5) in the dose-reduced group. Chemotherapy dose reduction was not associated with a statistically significant difference in OS (HR = 1.17, 95% CI 0.95-1.44, P = 0.132).For PFS, the median PFS after IPTW adjustment was 25.0months (95% CI 20.7-31.0) in the dose-maintained group and 20.5months (95% CI 17.1-26.9) in the dose-reduced group. Chemotherapy dose reduction was associated with a modest but statistically significant decrease in PFS (HR = 1.19, 95% CI 1.00-1.40, P = 0.047). Within the dose-reduced group, exploratory analyses suggested that patients whose first dose reduction occurred at cycle ≥ 3 had significantly better PFS and OS than those whose first dose reduction occurred during cycles 1-2.Treatment-related adverse events were broadly comparable between groups, with no statistically significant reduction observed in the dose-reduced group. In this multicenter real-world cohort of patients with LS-SCLC treated with definitive cCRT, chemotherapy dose reduction was not associated with a statistically significant difference in OS after IPTW adjustment but was associated with a modestly shorter PFS. Given the absence of an apparent reduction in treatment-related toxicity, chemotherapy dose reduction should not be considered an ideal strategy when full-dose treatment is feasible, although it may remain a pragmatic option for selected patients with limited treatment tolerance. The exploratory association between early dose reduction and poorer survival should be interpreted cautiously, as it may reflect greater frailty or poorer treatment tolerance rather than a direct causal effect of dose-reduction timing.

Weight-Based Chemotherapy Dosing in Obese Patients With Cancer: Back to the Future