Optimal Relative Dose Intensity Research Articles

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

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). 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. 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. 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 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.

Physical Fitness and Chemotherapy Tolerance in Patients with Early-Stage Breast Cancer.

ABSTRACTIntroductionAn optimal relative dose intensity (RDI) of adjuvant chemotherapy is associated with better survival in patients with breast cancer. Little is known about the role of physical fitness in attaining an adequate RDI in patients with early-stage breast cancer. We investigated the association between pretreatment physical fitness and RDI in this population.MethodsWe pooled individual patient data from two randomized exercise trials that studied exercise programs in early breast cancer: the Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (n = 230) and the Physical Activity during Chemotherapy Treatment (n = 204) study. Logistic regression models were used to evaluate the association between pretreatment fitness and achieving an optimal RDI (≥85%). In addition, we added an interaction term to the model to explore the potential moderating effect of participating in an exercise program.ResultsData were available for 419 patients (mean age at diagnosis, 50.0 ± 8.6 yr). In the total sample, lower pretreatment physical fitness was associated with significantly lower odds of achieving ≥85% RDI: age-adjusted odds ratio (OR) of 0.66 (95% confidence interval (CI), 0.46–0.94). In patients allocated to the supervised exercise intervention during chemotherapy (n = 173), the association between pretreatment physical fitness and RDI was almost completely mitigated (OR, 0.95 (95% CI, 0.54–1.56)), whereas it was more pronounced in patients who received care as usual (n = 172; OR, 0.31 (95% CI, 0.13–0.63); Pinteraction = 0.022).ConclusionsEarly-stage breast cancer patients with relatively lower levels of pretreatment physical fitness have lower odds of achieving an optimal dose of chemotherapy. Given that physical fitness is modifiable and our results suggest that following a moderate-to-high intensity exercise training during chemotherapy could improve treatment completion, clinicians should not refrain from referring patients to supportive exercise programs because of low fitness.

Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patients

BackgroundThe National Comprehensive Cancer Network (NCCN) guidelines have recommended tailored chemotherapy for stage III high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) colon cancer since 2018. Studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on stage III colon cancer survival, however, none has performed a stratified analysis by risk profiles. This study aims to identify the FOLFOX optimal RDI for high-risk and low-risk stage III colon cancer patients. MethodsData on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by 8 population-based cancer registries. Multivariable Cox model and Fine-Gray competing risks model were employed to explore Optimal RDI defined as the lowest RDI administered without significant differences in either overall or cause-specific death. ResultsAmong the 168 high-risk patients, the optimal RDI cut-off was 70% (HR = 1.59 with 95% CI: 0.69-3.66 in overall mortality; HR = 1.24 with 95% CI: 0.42-3.64 in cause-specific mortality when RDI < 70% vs. RDI ≥ 70%). Among the 239 low-risk patients, none of the evaluated cut-offs were associated with significant differences in risk of death between comparison groups. The lowest assessed RDI was 45%, HR = 0.80; 95% CI: 0.24 to 2.73 for overall mortality and HR = 0.53; 95% CI: 0.06 to 4.95 for cause-specific mortality, when RDI <45% versus RDI ≥45%. ConclusionsThere is no significant harm on the risk of death when reducing RDI by <30% for high-risk patients. For the low-risk patients, we found that RDI as low as 45% did not significantly affect the risk of death.

The effect of reduced RDI of chemotherapy on the outcome of breast cancer patients

The aims of this study were to investigate the impact of the relative dose intensity (RDI) of chemotherapy on disease-free survival (DFS) and overall survival (OS), to identify the optimal RDI cut-off points with the docetaxel, epirubicin and cyclophosphamide (TEC) regimen for stage I–III breast cancer patients and to explore the adverse events in these patients. To achieve this, we performed a retrospective analysis of breast cancer patients treated at the First Affiliated Hospital of Chongqing Medical University in 2011. The results showed that among 293 patients with the TEC regimen, 85% and 80% were the cut-off points at which a high RDI was associated with better overall survival (HR = 2.04; 95% CI 1.13, 3.70; p = 0.02) and disease-free survival (HR = 1.97; 95% CI 1.14–3.42; p = 0.02), respectively. Among 169 HR(+) patients, 80% was the cut-off point for DFS (HR = 2.33; 95% CI 1.07–5.08; p = 0.03), and 85% was the cut-off point for OS (HR = 3.00; 95% CI 1.24–7.26; p = 0.02). Among 105 HR(−) patients, 80% was the cut-off point for OS (HR = 2.86; 95% CI 1.05–7.80; p = 0.04). Of 293 patients, neutropenia, nausea, and vomiting were found to be correlated with the level of RDI. In conclusion, a higher RDI of chemotherapy is associated with better survival but with a higher probability of causing adverse events. To optimize survival benefits, the RDI should be maintained ≥ 85% for HR(+) patients and ≥ 80% for HR(−) patients.

Relative dose intensity and pathologic response rates in HIV-infected and HIV-uninfected breast cancer patients who received neoadjuvant chemotherapy.

e19140 Background: HIV-infected (HIV+) breast cancer patients may have significantly worse survival compared to HIV-uninfected (HIV-). If so, identifying the underlying mechanism might lead to effective interventions to reduce the disparity. Relative dose intensity (RDI) &lt; 0.85 has been associated with worse survival outcomes in non-metastatic breast cancer patients. We aimed to determine if RDI of chemotherapy and pathologic complete response (pCR) rates were lower for HIV+ patients who received neoadjuvant chemotherapy (NAC) compared with HIV-. Methods: We conducted a prospective cohort study in newly diagnosed breast cancer patients with locally advanced disease who initiated NAC at Princess Marina Hospital in Botswana between 2/2017 and 9/2019. Clinical and treatment data were collected at baseline and at every treatment visit. Surgical pathology post-NAC was graded as pCR if there was no invasive disease in the breast or lymph nodes. RDI was calculated for each patient, with optimal RDI ≥ 0.85. Dichotomous variables were compared using Fisher’s exact and chi-squared tests; and continuous variables using rank sum tests. Results: 111 patients were enrolled, of whom 84 (75.7%) were HIV-, 26 (23.4%) HIV+ and 1 (0.9%) with unknown status who was excluded from final analysis. HIV+ patients were less likely to receive optimal RDI (0.74 vs. 0.88; p = 0.03). Of the 110 patients 15 (13.6%) were still receiving chemotherapy; 22 (20%) prematurely discontinued chemotherapy of whom 11 (10%) received surgery; 7 (6.4%) completed chemotherapy but had no surgery. 77 (70%) completed surgery which included 11 (10%) with no pathology reports available, 3 (2.7%) inadequate surgical specimens and 63 (57.3%) complete pathology results included in pCR analysis: 1/13 (7.7%) HIV+ patients had a pCR compared to 12/50 (24%) in HIV-(p = 0.27). Conclusions: HIV+ patients were significantly more likely to receive inadequate neoadjuvant chemotherapy dose intensity, and trended towards a lower pCR in this small cohort, which may contribute to adverse treatment outcomes. Further study needed to validate high rate of treatment discontinuation and specific risk factors to inform targeted interventions to improve therapy delivery.

Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings.

Background: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. Methods: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. Results: Fourteen patients were Child–Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI ≥67.0% group, OS was significantly better than in the 8-week RDI <67.0% group (p = 0.003). Conclusions: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

Inverse relationship between reduced fatigue and severity of anemia in oncology patients treated with integrative medicine: understanding the paradox.

To assess the impact of integrative medicine (IM) on cancer-related fatigue in patients undergoing chemotherapy for early and advanced breast and gynecological (ovarian, endometrial, and cervical) cancer. Patients reporting significant levels of fatigue (on the Edmonton Symptom Assessment Scale (ESAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), or Measure Yourself Concerns and Wellbeing questionnaire (MYCAW)) were offered complementary and integrative medicine (CIM) treatments in addition to standard supportive care. Patients who did not undergo IM treatments were designated as controls. Attending at least five CIM treatments less than 30days between each session was considered as high adherence to integrative care (AIC). Of 258 eligible patients reporting significant fatigue, follow-up assessment at 6 and 12weeks was considered optimal for 120 patients in the intervention group and for 64 controls; 88 of treated patients found to be adherent to the IM intervention. At 12weeks, ESAS (P < 0.001) and EORTC (p = 0.001) scores for fatigue improved more significantly in treated patients, with a higher percent with optimal relative dose intensity in the AIC subgroup, both at 6weeks (P = 0.002) and at 12weeks (P < 0.001). IM treatment was paradoxically associated with a greater decrease in hemoglobin levels at 12weeks (P = 0.016), more so in the AIC subgroup (P = 0.024). Integrative medicine program may alleviate cancer-related fatigue in patients with breast and gynecological cancer undergoing chemotherapy.

Maintaining Dose Intensity of Adjuvant Chemotherapy in Older Patients With Breast Cancer

IntroductionMaintaining the relative dose intensity (RDI) of adjuvant chemotherapy at ≥ 85% has been associated with improved treatment outcomes in early-stage breast cancer (ESBC). Increasing evidence has suggested that patients aged ≥ 65 years can maintain the optimal RDI for standard chemotherapy regimens. The present study investigated the RDI of newer adjuvant chemotherapy regimens in this demographic. Patients and MethodsWe retrospectively analyzed the data from 281 patients aged ≥ 65 years with a diagnosis of ESBC who had received adjuvant chemotherapy across 3 sites in Queensland, Australia from 2010 to 2015. The primary endpoint was the proportion of patients who had received an RDI of ≥ 85%. ResultsThe median age at diagnosis was 68 years (range, 65-85 years), with 36.3% aged > 70 years. The patient characteristics included tumor stage T3 or T4 in 17% and node-positive disease in 60%. The common chemotherapy regimens included docetaxel/cyclophosphamide (23%), 5-fluorouracil/epirubicin/cyclophosphamide plus docetaxel or paclitaxel (17%); Adriamycin/cyclophosphamide/weekly paclitaxel (38%); and docetaxel/carboplatin/trastuzumab (11%). Primary (15%) and secondary (54%) granulocyte colony-stimulating factor (G-CSF) was used. An RDI of ≥ 85% was achieved in 63% of the patients. Significant associations were noted between a reduced RDI and age ≥ 70 years (P < .001), Charlson comorbidity index ≥ 1 (P = .043), initial dose reductions (P = .01), secondary G-CSF use (P = .45), hospital admission (P < .001), and febrile neutropenia (P = .007). Treatment-related toxicities were the most common reason for noncompletion, with high rates of hospital admissions (46%) and febrile neutropenia (22%). ConclusionOur findings suggest that patients aged ≥ 65 years with ESBC can maintain an optimal RDI with modern chemotherapy regimens. Appropriate geriatric assessment and the use of supportive measures such as G-CSF could better assist select groups to maintain an optimal dose intensity.

Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2-breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI<85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR=1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR=2.64; 95% CI 1.09, 6.38) and overall survival (HR=2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained≥85% in ER+/PR+, HER2- patients, and≥75% in TNBC patients.

Relative dose intensity in early stage breast cancer chemotherapy: A retrospective analysis of incidence, risk factors and outcomes at a south‐west Sydney cancer clinic

In early stage breast cancer chemotherapy relative dose intensity (RDI) of <85% leads to poorer outcomes. This study assesses what proportion of such patients at a south-west Sydney cancer clinic received optimal RDI and the reasons and risk factors contributing to RDI reduction, as well as comparing survival outcomes. A retrospective analysis of 308 patients treated with adjuvant chemotherapy for early stage breast cancer at the Macarthur Cancer Centre was undertaken, with an overall RDI calculated for each patient. The study analysed reasons for reductions in RDI as well as predictive factors for reduced RDI and overall and disease-free survival. Mean RDI was 92%. Of the participants, 17% had an RDI less than 85%, 55% received 100% RDI. Hematological toxicity, infection and patient choice were the most common reasons for RDI reduction. Body surface area capping (BSA) was the most common cause of initial dose reduction. Obesity, increasing body mass index and age ≥65 years were risk factors for RDI reduction. Disease-free and overall survival were reduced with RDI < 50%; overall survival decreased when RDI < 65%. Most patients attained the RDI benchmark; however dose intensity reducing events occurred frequently. Despite contrary recommendations in the literature, BSA capping and dose reduction due to patient choice were common. Implementation of focused patient and physician education strategies may improve these results, as could measures directed as supporting those at risk (i.e. elderly or obese).