Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. METHODS: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. RESULTS: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Reduction in chemotherapy relative dose intensity decreases overall survival of neoadjuvant chemoradiotherapy in patients with locally advanced esophageal carcinoma.

BACKGROUND: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. METHODS: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). CONCLUSION: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.

Lenvatinib plus Pembrolizumab Combination Therapy for Advanced or Recurrent Endometrial Cancer: A Single-Center, Retrospective Analysis.

A multi-kinase inhibitor, lenvatinib, plus an immune checkpoint inhibitor, pembrolizumab, became a viable therapeutic option for advanced or recurrent endometrial cancer in Japan by the end of 2021. The Japanese population has a relatively unique genetic background. Hence, the safety profile and effectiveness of lenvatinib plus pembrolizumab may differ between the Japanese and other populations. This single-center, retrospective study aimed to evaluate the treatment efficacy of lenvatinib plus pembrolizumab and the safety profile of the associated adverse events. The clinical records of 15 patients, who received lenvatinib plus pembrolizumab for advanced or recurrent endometrial cancer at the Tohoku University Hospital, were reviewed. Best overall response and disease control rates were 40.0% and 73.3%, respectively. Treatment was discontinued owing to disease progression and adverse events in six patients, respectively. As of the end of July 2023, treatment was ongoing in the remaining three patients. The median treatment and progression-free survival durations were 118 and 258 days, respectively. Relative dose intensity of lenvatinib was not positively associated with progression-free survival, neither during the first 4 weeks after treatment initiation nor during the entire treatment period. All patients experienced one or more adverse events, the most common of which were hypothyroidism (90%) and hypertension (83.3%). Among the 15 patients, 13 required lenvatinib dose reduction owing to adverse events. One patient developed grade 4 interstitial pneumonia requiring intensive care. Our results validate the short-term efficacy of lenvatinib plus pembrolizumab, and indicate that dose optimization of lenvatinib could be individualized without impairing efficacy.

Clinical characteristics and survival outcomes of elderly patients with de novo metastatic germ cell tumors.

OBJECTIVES: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy. METHODS: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities. RESULTS: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy. CONCLUSIONS: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy.

Impact of Relative Dose Intensity of Docetaxel, Cisplatin, and 5-Fluorouracil Neoadjuvant Chemotherapy on Survival of Esophageal Squamous Cell Cancer Patients.

INTRODUCTION: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. RESULTS: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1-0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. CONCLUSION: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

BACKGROUND: Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. METHODS: This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. RESULTS: An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20 weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). CONCLUSIONS: This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

Relative dose intensity of taxane-based chemotherapy in breast cancer patients in a tertiary hospital.

INTRODUCTION: Breast cancer (BC) is the most diagnosed tumor among women worldwide. The aim of this study was to investigate the incidence and causes of low relative dose intensity (RDI) < 85% for taxane-based chemotherapy regimens used in the treatment of BC in Sultan Qaboos University Hospital (SQUH). METHODS: This was a retrospective study that included 303 BC patients, treated with taxane-based chemotherapy protocols at SQUH. RDI was calculated for each chemotherapy regimen and causes and predictors of low RDI < 85% were identified. Prophylactic and therapeutic supportive measures for certain toxicities were studied. RESULTS: 50.8% of the patients had neoadjuvant chemotherapy, 38% had adjuvant chemotherapy, and 11.2% of patients were given palliative treatment. AC-T and AC-THP were the most used regimens (40.3% and 17.2%). Mean RDI of used taxane-based chemotherapy regimens was 93.4%. Dose delays, dose reductions, and treatment discontinuation occurred in 36.6%, 14.8%, and 11.5%, respectively. Thirty-eight patients (12.5%) had low RDI < 85% which was reduced to 9.9% after the use of an alternative taxane. Age and chemotherapy intent were significant risk factors. 83.8% received primary granulocyte colony stimulating factor. CONCLUSION: An optimal RDI greater than 85% was achieved in most cases. Furthermore, prophylactic and therapeutic supportive measures were widely used.

Impact of relative dose intensity on pathologic complete response in human epidermal growth factor receptor 2 positive breast cancer patients receiving neoadjuvant TCHP.

PURPOSE: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. METHODS: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. RESULTS: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. CONCLUSIONS: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.

The influence of body mass index on the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy in women with early-stage breast cancer.

PURPOSE: To investigate the influence of body mass index (BMI) on the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy in early breast cancer patients. METHODS: Early-stage breast cancer patients who received (neo)adjuvant weekly paclitaxel 80 mg/m2 chemotherapy were included in this retrospective study. Patients were divided into three groups based on their BMI: lean, overweight, and obese. Logistic regression was used to assess for association between BMI with administered relative dose intensity (RDI) < 85%. The occurrence of treatment modifications and the pathological response on neoadjuvant chemotherapy were compared between BMI categories. RESULTS: Four hundred (400) patients were included in this study; 200 (50%) lean, 125 (31%) overweight, and 75 (19%) obese patients. The adjusted odds ratio to receive RDI < 85% for BMI was 1.02 (p value, .263). Treatment modifications occurred in 115 (58%), 82 (66%), and 52 (69%) patients in the respective BMI categories (p value = .132). Peripheral neuropathy was observed in 79 (40%), 58 (46%), and 41 (55%) patients in the lean, overweight, and obese group (p value = .069), whereas hematologic toxicity was observed in 31 (16%), 10 (8%), and 4 (5%) patients (p value = .025). Pathological complete response was observed in 22 (17%), 11 (14%), and 6 (13%) patients in the respective BMI categories (p value = .799). CONCLUSION: BMI did not significantly influence the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy. Therefore, the results of this study align with current guideline recommendations of using full-weight-based paclitaxel chemotherapy in obese patients.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. METHODS: Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. RESULTS: Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08-0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33-0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33-0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38-1.02, p = 0.06). CONCLUSIONS: In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Therapeutic efficacy of dose-reduced adjuvant chemotherapy with S-1 in patients with pancreatic cancer: a retrospective study.

BACKGROUND: S-1 adjuvant chemotherapy is the standard treatment in Asia for resectable pancreatic ductal adenocarcinoma. The relative dose intensity of adjuvant chemotherapy influences survival in pancreatic cancer but does not precisely reflect treatment schedule modifications. We investigated the effects of total dose intensity of S-1 adjuvant chemotherapy on the survival of patients with pancreatic cancer and the permissible dose reduction. METHODS: Patients who underwent surgical resection during 2011-2019 for pancreatic cancer were selected. We determined the total dose intensity cut-off value that predicted tumor recurrence within 2 years postoperatively using receiver operating characteristic curves and compared the outcomes between the high and low total dose intensity groups. RESULTS: Patients with total dose intensity ≥ 62.5% (n = 53) showed significantly better overall survival than those with total dose intensity < 62.5% (n = 16) (median survival time: 53.3 vs. 20.2 months, P < 0.001). The median survival of patients without adjuvant chemotherapy (total dose intensity = 0, n = 28) was 24.8 months. Univariate analysis identified lymphatic involvement (P = 0.035), lymph node metastasis (P = 0.034), and total dose intensity (P < 0.001) as factors affecting survival. On multivariate analysis, total dose intensity (P < 0.001) was an independent predictor of worse survival. CONCLUSIONS: Maintaining a total dose intensity of at least 60% in S-1 adjuvant chemotherapy seems important to achieve a long postoperative survival in patients with pancreatic cancer.

The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer.

BACKGROUND: An uninterrupted dose of oxaliplatin-based cytotoxic therapy is an essential component in the standard treatment regimen of metastatic colon cancer (mCC). Data on the impacts of dose intensity reduction on the palliative treatment for patients with mCC remain scarce. Hence, this study aimed to investigate the impact of palliative chemotherapy dose modifications (DM) on the survival of patients with mCC. METHODS: Patients with stage IV colon cancer who received first-line palliative FOLFOX regimen chemotherapy between 2014 until 2018 in the Oncology Department of the National Cancer Institute were conveniently sampled retrospectively to analyse the treatment efficacy. The cumulative dose and duration of chemotherapy received by the patients were summarised as relative dose intensity (RDI) and stratified as High RDI (RDI ≥ 70%) or Low RDI (RDI < 70%). Progression-free survival (PFS) and 2-year overall survival (OS) between the two groups were analysed using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Out of the 414 patients identified, 95 patients with mCC were eligible and included in the final analysis. About half of the patients (n = 47) completed the 12-cycle chemotherapy regimen and one patient received the complete (100%) RDI. The overall median RDI was 68.7%. The Low RDI group (n = 49) had a 1.5 times higher mortality risk than the High RDI group [OS, Hazard Ratio (HR) = 1.5, 95% Cl: 1.19-1.82] with a significant median OS difference (9.1 vs. 16.0 months, p <  0.01). Furthermore, patients with lower dose intensity showed double the risk of disease progression (PFS, HR = 2.0, 95% CI: 1.23-3.13) with a significant difference of 4.5 months of median PFS (p <  0.01). Gender and RDI were the independent prognostic factors of both OS and PFS. CONCLUSION: Reduction in the dose intensity of palliative chemotherapy may adversely affect both disease progression and overall survival among mCC patients.

Optimal management of lenvatinib therapy for patients with unresectable hepatocellular carcinoma by balancing the therapeutic effect with the relative dose intensity.

AIMS: We aimed to assess the optimal management of first or later-line lenvatinib therapy (LEN) for patients with unresectable hepatocellular carcinoma (uHCC), by clarifying the difference of degree between relative dose intensity (RDI) to achieve objective response (OR) and disease control (DC) by aiming at stable disease (SD), taking dose modifications into consideration. METHODS: One hundred uHCC patients who received LEN in first- or later-line settings, between April 2018 and December 2020 in our hospital were analyzed retrospectively. The factors associated with overall survival (OS), time to progression (TTP), OR and DC were assessed. The optimal cut-off values of RDI 4 weeks after initiation of LEN (RDI during cycle 1) and total RDI (RDI during all cycles) to predict achievement of OR and DC by aiming at SD were determined by receiver operator curve analysis. RESULTS: Achievement of OR and SD were favorable factors for OS (HR, 0.080 and 0.20) and TTP (HR, 0.052 and 0.073), with progressive disease defined as the reference. RDI ≥ 0.8 during cycle 1 and RDI ≥ 0.4 during cycle 1 contributed to achievement of OR (odds ratio, 3.28) and DC (odds ratio, 4.85), respectively. Experience of dose interruption was associated with a favorable TTP (HR, 0.58). The therapeutic line of LEN did not contribute to OS, TTP or best response. CONCLUSIONS: To achieve OR and SD for a favorable outcome of first- or later-line LEN, high and moderate early-phase RDI are required, respectively. The degree of RDI during LEN and tolerance need compatible by dose modifications.

Can integrative oncology increase adherence to chemotherapy in advanced gynecologic cancer?

OBJECTIVE: Integrative oncology (IO) has been shown to improve quality-of-life (QoL) and increase adherence to planned chemotherapy regimens. This study examined the impact of a patient-tailored IO program on adherence to chemotherapy among patients with advanced gynecological cancer. METHODS: This prospective non-randomized, pragmatic, preference study examined patients with stage III/IV gynecological cancers undergoing 6 weeks of weekly IO treatments. Adherence to the planned chemotherapy regimen was assessed using the relative dose intensity (RDI) calculation. Patients consistently attending IO treatments (consistent-IO group) were compared to those who were not (non-consistent IO group). RESULTS: RDI was calculated for 73 patients in the consistent-IO group (99 chemotherapy cycles) and 61 in the non-consistent-IO group (96 cycles with IO care, 126 cycles without). Both groups had similar baseline demographic characteristics, with endometrial cancer more prevalent in the consistent-IO group. RDI was significantly less reduced in the consistent-IO chemotherapy group (p = 0.005). During taxane-based regimens, RDI was better maintained in the consistent-IO group (0.93 vs. 0.87, p = 0.012), though not with platinum-based cycles. Linear regression model found a correlation between preserved RDI and consistent attendance at weekly IO treatments, and lower rates of chemotherapy-induced peripheral neuropathy and pain. CONCLUSION: Patient-tailored IO programs for patients with advanced gynecological cancer may help preserve adherence to chemotherapy at 6 weeks, especially with taxane-based regimens. Further research needs to explore whether this correlation is chemotherapy agent-specific.

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer.

PURPOSE: Carboplatin (CBDCA) + nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the most effective chemotherapeutic regimens for advanced non-small cell lung cancer (NSCLC) treatment. However, neutropenia and neuropathy are well-known dose-limiting toxicities associated with this regimen, frequently resulting in treatment suspension and dose reduction. In the present study, we aimed to identify risk factors associated with CBDCA + nab-PTX treatment suspension. METHODS: Patients with NSCLC who received CBDCA + nab-PTX ± atezolizumab or pembrolizumab regimens were retrospectively evaluated. The risk factor(s) for treatment suspension and primary causes underlying suspension during the first course were assessed; the relative dose intensity (RDI) was compared between patients with and without identified factors. RESULTS: The frequency of treatment suspension was determined as 55%. The causes for suspension were neutropenia (65.2%), infection (24.2%), thrombocytopenia (6.1%), and other conditions. The calculated RDI was 98.5% for CBDCA and 79.3% for nab-PTX. Based on univariate and multivariate analyses, grade 1 or higher liver dysfunction was identified as a risk factor for treatment suspension. We determined primary causes for treatment suspension as neutropenia and/or infection, as they are closely related. Next, we evaluated associated factors and determined age ≥65 years and performance status (PS) 2 as potential factors, in addition to liver dysfunction. CONCLUSION: We observed that liver dysfunction at baseline is a risk factor for treatment suspension. In addition, age ≥65 years and PS 2 can result in treatment suspension owing to neutropenia and/or infection during CBDCA + nab-PTX treatment.

Extending Treatment Intervals of R-CHOP Therapy Might Be Acceptable for Some Patients with Non-indolent Non-Hodgkin's B-cell Lymphoma.

R-CHOP therapy is generally performed every 3 weeks. We investigated the effects of extending the interval of R-CHOP therapy for > 1 week on the prognoses of patients with non-indolent non-Hodgkin's B-cell lymphoma. Among the 338 patients with non-indolent non-Hodgkin's B-cell lymphoma who received initial chemotherapy at our institution, we focused on 178 patients who received R-CHOP therapy and analyzed the outcomes of the patients stratified by the treatment intervals. The estimated 3-year overall survival (OS) for the entire population was 82.1%. Patients treated at intervals of ≥ 4 weeks were significantly older, and they had significantly longer follow-up periods and lower relative dose intensity. But the estimated 3-year OS was comparable to those treated at <4 weeks (83.3% vs. 80.5% p=0.947). In a multivariate analysis, age and the dose of anti-cancer agents had significant impacts on OS, but there was no significant relationship regarding the treatment intervals. Propensity score matching confirmed the same result. R-CHOP therapy every around 4 weeks could achieve relatively good survival in some selected patients with non-indolent non-Hodgkin's B-cell lymphoma.

Association of the Geriatric 8 with treatment intensity and prognosis in older patients with diffuse large B-cell lymphoma.

Because of the heterogeneity among older patients with diffuse large B-cell lymphoma (DLBCL), the establishment of an easy-to-use geriatric assessment tool is an unmet need. We verified the impact of the Geriatric 8 (G8) on treatment stratification and overall survival (OS). We conducted a retrospective, multicentre analysis of older patients (≥65 years) with DLBCL. The primary endpoint was OS. The total average relative dose intensity (tARDI) was defined as the average delivered dose intensity divided by the planned dose intensity through all cycles. A total of 451 patients were diagnosed with DLBCL from 2007 to 2017, and 388 patients received standard regimens. A multivariate Cox model confirmed that the G8 was a significant predictor of OS (hazard ratio 0·88, 95% confidence interval 0·828-0·935). A Cox model with restricted cubic spline showed a linear association between the G8 and the mortality risk. The G8 had a significant impact on OS in elderly patients with DLBCL. The upper limit of tARDI for standard regimens to improve OS might be appropriate at ≥80% for patients with high G8 scores and 60% for patients with low G8 scores. However, the standard regimens should be given to all patients regardless of the G8 score to improve OS.

Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Chemotherapy-induced toxicities lead to therapy dose reduction or delay, affecting patient outcomes. This systematic review and meta-analysis evaluated the impact of relative dose intensity (RDI) on survival in adult patients with solid tumor cancer on nonadjuvant-based chemotherapy regimens. METHODS: PubMed, Embase, and Web of Science databases were searched for peer-reviewed English journal articles or congress abstracts evaluating association between RDI and survival; observational studies, case series of ≥20 patients, and clinical trials published between 2013 and 2020 were eligible. Meta-analyses were conducted to quantify the association between RDI levels and overall survival (OS) among studies reporting a hazard ratio (HR) for OS by similar tumor types, regimens, and RDI. Forest plots represented summary HR and 95% confidence interval (CI); Cochran's Q and I2 tests evaluated study heterogeneity. RESULTS: Overall, 919 articles were reviewed and 22 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80% versus ≥80% and <85% versus ≥85% was observed upon meta-analysis of four carboplatin-based studies for breast, non-small cell lung, or ovarian cancer (HR 1.17; 95% CI: 1.07-1.27) and three FOLFOX-, FOLFIRI-, or FOLFIRINOX-based studies for colorectal or pancreatic cancer (HR 1.39; 95% CI: 1.03-1.89). Grade 3 or higher hematologic toxicities were higher for carboplatin-based regimens (thrombocytopenia: 14%-22%; anemia: 15%-19%; neutropenia: 24%-58%) than FOLFOX-, FOLFIRI-, or FOLFIRINOX-based regimens (thrombocytopenia: 1%-4%; anemia: 5%-19%; neutropenia: 19%-47%). CONCLUSION: The results suggested longer OS with RDI ≥80% or ≥85% for both regimens, indicating that management of toxicities across treatment modalities may contribute to maintenance of higher RDI and benefit survival for patients with advanced solid tumors. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced toxicities lead to dose reduction and/or treatment delay, thus affecting patient outcomes. Results of this systematic review and meta-analysis, evaluating the impact of relative dose intensity (RDI) on survival of patients with solid tumors on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for patients with solid tumors on carboplatin-based and FOLFOX-, FOLFIRI-, or FOLFIRINOX-based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80% or ≥ -85%. Although grade 3 or higher hematologic toxicities occurred more in carboplatin-based studies, managing toxicities across treatment regimens may contribute to maintenance of higher RDI and ultimately benefit overall survival.

Association of relative dose intensity with BMI and pathologic complete response in patients treated with neoadjuvant chemotherapy for breast cancer.

PURPOSE: Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than patients with high BMI, explaining the mechanism for the association between BMI and pCR. METHODS: We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer at Yale New Haven Hospital-Smilow Cancer Hospital. We reviewed medical records to determine tumor characteristics, chemotherapy doses, and reasons for dose reductions or delays. The treatment RDI was calculated using published methods. Chi-squared analyses were conducted to determine the associations between RDI and BMI and between RDI and pCR. RESULTS: Our cohort (n = 237) had an average age of 53 years (SD 13) and mean BMI of 29.5 kg/m2 (SD 7.0). Fifty-eight patients (24%) received <85% RDI, and 61% of patients experienced at least one dose reduction or delay. BMI was not associated with RDI (p = 0.71), and RDI was not associated with pCR (p = 0.31); however, fewer dose delays was associated with pCR (p = 0.02). The most common reasons for dose reduction or delays were neuropathy, myelosuppression, and personal reasons. CONCLUSIONS: Nearly one quarter of our cohort had RDI <85%. Although RDI overall was not associated with pCR, having fewer dose delays was associated with pCR. Our results highlight a need for improved patient adherence to and tolerability of neoadjuvant chemotherapy to minimize treatment delays.