Dose Adjuvant Chemotherapy Research Articles

The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non–small-cell lung cancer (NSCLC).

TPS8116 Background: Pembrolizumab (pembro; anti–PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309–1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145–0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II–IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1–4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS ( < 1% vs 1%–49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). The abstract was originally presented and published in: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281. Clinical trial information: NCT06077760 .

Elective Irradiation of Retropharyngeal Lymph Nodes as an Indication for Adjuvant Radiation Therapy After Transoral Surgery for Tonsil Cancer

Treatment of squamous cell carcinoma of the tonsil involves primary radiation therapy (RT) or surgical resection. Historically, if RT was the primary or adjuvant treatment modality, most of the bilateral retropharyngeal lymph nodes (RPLNs) were treated electively with a therapeutic dose for subclinical disease, regardless of whether radiographically pathologic lymph nodes were seen on initial diagnostic imaging. De-escalation strategies include the incorporation of transoral surgery with the goal to either eliminate or reduce the dose of adjuvant RT or chemotherapy. Transoral surgery does not include elective removal of the RPLNs, and no guideline or outcome paper recommends adjuvant RT specifically to electively treat RPLNs. In this Topic Discussion, we discuss pertinent literature and suggest management decisions. The management decisions discussed in this Topic Discussion pertain to only tonsillar primaries and not those of the soft palate or base of the tongue.

Abstract CT281: The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC)

Abstract Background: Pembrolizumab (pembro; anti-PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309-1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145-0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II-IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1-4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS (<1% vs 1%-49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). Citation Format: Jonathan D. Spicer, Santosh M. Nair, Adnan Khattak, Jay M. Lee, Michelle Brown, Robert S. Meehan, Nazly Shariati, Xuan Deng, Ayman Samkari, Jamie E. Chaft. The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281.

Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer

PurposeThe optimal time to initiation of adjuvant chemotherapy (TTAC) for triple negative breast cancer (TNBC) patients is unclear. This study evaluates the association between TTAC and survival in TNBC patients.MethodsWe conducted a retrospective study using data from a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018, registered in the Tumor Centre Regensburg was conducted. Data included demographics, pathology, treatment, recurrence and survival. TTAC was defined as days from primary surgery to first dose of adjuvant chemotherapy. The Kaplan–Meier method was used to evaluate impact of TTAC on overall survival (OS) and 5-year OS.ResultsA total of 245 TNBC patients treated with adjuvant chemotherapy and valid TTAC data were included. Median TTAC was 29 days. The group receiving systemic therapy within 22 to 28 days after surgery had the most favorable outcome, with median OS of 10.2 years. Groups receiving systemic therapy between 29–35 days, 36–42 days, and more than 6 weeks after surgery had significantly decreased median survival, with median OS of 8.3 years, 7.8 years, and 6.9 years, respectively. Patients receiving therapy between 22–28 days had significantly better survival compared to those receiving therapy between 29–35 days (p = 0.043), and patients receiving therapy after 22–28 days also demonstrated significantly better survival compared to those receiving therapy after more than 43 days (p = 0.033).ConclusionTiming of adjuvant systemic therapy can influence OS in TNBC patients. Efforts should be made to avoid unnecessary delays in administering chemotherapy to ensure timely initiation of systemic therapy and optimize patient outcomes.

Adjuvant chemotherapy or no adjuvant chemotherapy? A prediction model for the risk stratification of recurrence or metastasis of nasopharyngeal carcinoma combining MRI radiomics with clinical factors.

Dose adjuvant chemotherapy (AC) should be offered in nasopharyngeal carcinoma (NPC) patients? Different guidelines provided the different recommendations. In this retrospective study, a total of 140 patients were enrolled and followed for 3 years, with 24 clinical features being collected. The imaging features on the enhanced-MRI sequence were extracted by using PyRadiomics platform. The pearson correlation coefficient and the random forest was used to filter the features associated with recurrence or metastasis. A clinical-radiomics model (CRM) was constructed by the Cox multivariable analysis in training cohort, and was validated in validation cohort. All patients were divided into high- and low-risk groups through the median Rad-score of the model. The Kaplan-Meier survival curves were used to compare the 3-year recurrence or metastasis free rate (RMFR) of patients with or without AC in high- and low-groups. In total, 960 imaging features were extracted. A CRM was constructed from nine features (seven imaging features and two clinical factors). In the training cohort, the area under curve (AUC) of CRM for 3-year RMFR was 0.872 (P <0.001), and the sensitivity and specificity were 0.935 and 0.672, respectively; In the validation cohort, the AUC was 0.864 (P <0.001), and the sensitivity and specificity were 1.00 and 0.75, respectively. Kaplan-Meier curve showed that the 3-year RMFR and 3-year cancer specific survival (CSS) rate in the high-risk group were significantly lower than those in the low-risk group (P <0.001). In the high-risk group, patients who received AC had greater 3-year RMFR than those who did not receive AC (78.6% vs. 48.1%) (p = 0.03). Considering increasing RMFR, a prediction model for NPC based on two clinical factors and seven imaging features suggested the AC needs to be added to patients in the high-risk group and not in the low-risk group.

Evaluation of clinical effects of a multidisciplinary-collaborated cancer support team for gastrointestinal cancer chemotherapy: prospective observational study protocol of M-CAST study

BackgroundAlthough the multidisciplinary-collaborated team approach in cancer treatment has recently become popular, prospectively evaluated evidence is limited. We started a multidisciplinary-collaborated cancer support team (MCST) to facilitate cooperation across multidisciplinary medical staff in our hospital and established clinical evidence of supportive care. This study aimed to prospectively evaluate the clinical activity and effect of MCST in patients with gastrointestinal cancer receiving chemotherapy.MethodsThis is a single-center, single-arm, observational study. Patients with gastrointestinal cancer scheduled to receive chemotherapy are enrolled and supported by the MCST. The primary endpoints are the number of interventions by medical staff and the number of patients who showed improvement in side effects. The secondary endpoints are the severity of side effects, medical expenses, number of consultations, the acceptance rate of prescription recommendations, adjuvant chemotherapy completion rates, dose intensity, and time required for co-medical intervention. In addition, medical staff and attending physicians evaluate all adverse events.DiscussionThis study is expected to contribute to establishing new cancer-supportive care teams for patients with gastrointestinal cancer receiving chemotherapy and those with cancer receiving chemotherapy.Trial registrationThis trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCT1030220495.The date of first registration, 29/11/2022, https://jrct.niph.go.jp/search

Short-course neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer: A multicenter randomized phase-II trial (NORPACT-1).

LBA4005 Background: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has shown improved survival in metastatic pancreatic cancer, and promising results as downstaging chemotherapy in locally advanced pancreatic cancer. The efficacy of neoadjuvant FOLFIRINOX in patients with resectable pancreatic cancer is unknown. Methods: This is a randomized phase II trial with patients included from 12 Nordic centers in the period 2017-2021. Patients with resectable pancreatic head cancer were randomly assigned to receive either four neoadjuvant cycles of FOLFIRINOX followed by surgery and eight adjuvant cycles mFOLFIRINOX, or upfront surgery and adjuvant mFOLFIRINOX (12 cycles). The primary endpoint was overall survival at 18 months after date of randomization (intention-to-treat [ITT]). Overall survival was estimated with the Kaplan-Meier method, and differences between the respective treatment arms were analyzed with log rank tests. Results: In NORPACT-1, 140 patients were randomly assigned (neoadjuvant chemotherapy, n=77;upfront surgery, n=63). Median age was 66.5 years (IQR 59, 72), while 115 (82.1%) and 25 (17.9%) patients were ECOG 0 and 1, respectively. Median OS by ITT was 25.1 months [95% CI 17.2-34.9] with neoadjuvant chemotherapy and 38.5 months [95% CI 27.6-not reached] with upfront surgery (p=0.096). The proportion of patients alive at 18 months by ITT was 59.7 % [95% CI 48.9-70.7] and 73.0 % [95% CI 62.0-84.0], respectively (p=0.100). Resection rates were 81.8% (63/77) in the neoadjuvant group and 88.9% (56/63) in the upfront surgery group (p=0.342). In the neoadjuvant group 61 (79.2%) patients initiated neoadjuvant FOLFIRINOX. Completion of the four planned cycles was 60%, with dose reductions and delays in 70% and 28.3%. Per-protocol (PP) analysis of 60 patients with pancreatic ductal adenocarcinoma (PDAC) who received minimum one cycle neoadjuvant FOLFIRINOX compared with 55 patients in the upfront surgery arm who were explored showed median OS of 23.0 months [95% CI 16.2-34.9] and 34.4 months [95% CI 19.4-not reached] (p=0.158). Adjuvant chemotherapy initiation rate was 66.2% and 74.6% (p=0.282) by ITT. In resected PDAC patients the rate was 86.4% and 89.8% (p=0.593). Of 120 patients receiving at least one dose of neoadjuvant and/or adjuvant chemotherapy (safety population), 57.5% (42/73) in the neoadjuvant group and 40.4% (19/47) in the upfront surgery group experienced at least one grade ≥3 adverse event (p=0.067). In PP analysis neoadjuvant FOLFIRINOX was associated with significantly higher rate of N0 (p=0.002) and R0 resection (p=0.011). Conclusions: Neoadjuvant FOLFIRINOX did not improve OS compared with upfront surgery in resectable pancreatic head cancer. Our results do not support neoadjuvant chemotherapy as standard of care for these patients. Future trials should incorporate a biomarker-based design. Clinical trial information: NCT02919787 .

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

Abstract P1-01-03: The Impact of Comorbid HIV infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Breast Cancer Patients

Abstract Introduction In the South African Breast Cancer and HIV Outcomes (SABCHO) study, early-stage breast cancer patients living with HIV, compared to their HIV-negative counterparts, demonstrated higher overall mortality and lower rates of pathologic complete response if treated with neoadjuvant chemotherapy. We aimed to determine if comorbid HIV also impacted receipt of timely and complete neoadjuvant and adjuvant chemotherapy. Methods We retrospectively identified Black, stage I-III SABCHO participants diagnosed with breast cancer from June 2015 to July 2019 and who received at least 2 doses of neoadjuvant or adjuvant chemotherapy at either Charlotte Maxeke Johannesburg Academic Hospital (Gauteng) or Grey’s Hospital (KwaZulu-Natal). Data on the originally prescribed chemotherapy regimen and the dose and timing of all received chemotherapy was extracted from patients’ medical records, as well as values from all complete blood counts and metabolic panels performed during treatment. Relative dose intensity (RDI) was calculated for each agent in the prescribed regimen with the mean RDI of all agents representing the RDI of the full regimen. We assessed for associations between full regimen RDI and HIV status using a multivariable linear regression model that included demographic and clinical covariates also shown to impact RDI. We also compared rates of myelosuppression, alkaline phosphatase elevation, and creatinine elevation using linear regression. Using previously collected survival data, we compared overall mortality based on overall RDI above or below 0.85. Results We analyzed data from 325 eligible subjects, 166 of whom were living with HIV. No differences based on HIV status were appreciated in the prescribed chemotherapy regimens. For women without HIV median RDI was 0.87 (interquartile range (IQR) 0.77-0.94) and, in those living with HIV, it was 0.89 (IQR 0.77-0.95). HIV status showed no significant association with RDI on multivariable analysis, and the only patient characteristics associated with RDI were estrogen/progesterone receptor (ER/PR) and HER2 status. Patients living with HIV experienced more CTCAE v5.0 grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs 1.9%, p=0.001; leukopenia: 8.4% vs 1.9%, p=0.008) and were more likely to receive at least one dose of filgrastim (24.7% vs 10.7%, p=0.001). Receipt of RDI greater or less than 0.85 did not predict overall mortality in the full cohort or HIV status subgroups. A trend towards improved survival with RDI greater than 0.85 was seen among the 69 participants with ER/PR negative disease (hazard ratio: 0.60, 95% confidence interval: 0.30-1.21, p = 0.15). Conclusions Neoadjuvant and adjuvant chemotherapy RDI did not differ by HIV status among women in the SABCHO study, although women living with HIV experienced more myelotoxicity during treatment. Efforts to reduce chemotherapy dose reduction and delays should target all South African breast cancer patients. Citation Format: Daniel S. O’Neil, Oluwatosin A Ayeni, Hayley A. Farrow Woolridge, Wenlong Carl Chen, Georgia Demetriou, Ines Buccimazza, Sharon Cacala, Maureen Joffe, Michael Antoni, Gilberto Lopes, Yoanna Pumpalova, Witness Mapanga, Judith S. Jacobson, Katherine D. Crew, Alfred I. Neugut, Paul Ruff, Herbert Cubasch. The Impact of Comorbid HIV infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-01-03.

Cardiovascular Toxicity Induced by Vascular Endothelial Growth Factor Inhibitors.

Cardiotoxicity is an important side effect of vascular endothelial growth factor (VEGF) inhibitors therapy used in the treatment of various malignancies, leading to increased morbidity and mortality. Arterial hypertension, cardiac ischemia with the acceleration of atherosclerosis, arrhythmias, myocardial dysfunction and thromboembolic disease are the most feared cardiovascular adverse reactions due to VEGF inhibitors. Susceptibility for the occurrence of VEGF inhibitors-induced cardiotoxicity has multifactorial determinants, with a significant inter-individual variation. Baseline cardiovascular risk assessment of the patient, type and stage of cancer, dose and duration of VEGF inhibitors treatment and adjuvant chemotherapy or radiotherapy are the main predictors for cardiotoxicity. The role of the cardio-oncology team becomes essential for achieving maximum therapeutic anti-angiogenic effects with minimum cardiovascular side effects. This review will summarize the incidence, risk factors, mechanisms, management and treatment of VEGF inhibitors-induced cardiovascular toxicity.

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

BackgroundColorectal 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.MethodsPatients 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.ResultsFive 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).ConclusionsIn resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Survival Outcomes With Reduced Doses of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

There have not been enough recent studies investigating the incidence or efficacy of dose reduction in adjuvant chemotherapy for epithelial ovarian cancer. This study examined whether patients who needed dose reduction showed poorer survival outcomes. From 2011 to 2021, 102 patients were included in the study. Patients who underwent neoadjuvant chemotherapy and those with early-stage disease were excluded. Patients were divided into two groups: those who had a ≥60% dose reduction during the whole period of first-line adjuvant chemotherapy, and those with dose reductions <60%. Of the 102 patients, 38 (37.3%) underwent dose reduction ≥60%. PFS was significantly longer in the group whose dose reductions were ≥60%, whereas OS was not significant. A dose reduction of ≥60%, determined by patients' medical conditions, during first-line of adjuvant chemotherapy does not negatively influence survival outcomes, such as OS and PFS, in advanced epithelial ovarian cancer.

Immediate Adjuvant Chemotherapy in Non-Metastatic Colon Cancer: Phase I Trial Evaluating a Novel Treatment Protocol

BackgroundThe optimal timing of adjuvant chemotherapy (AC) in non-metastatic colon cancer is poorly defined. Delays in AC result in decreased survival. Effective cytotoxic treatments should be considered during the perioperative phase of care. The immediate adjuvant chemotherapy (IAC) concept intends to capitalize on the therapeutic benefits that can be achieved in the perioperative period. We aim to demonstrate that IAC is safe and tolerable. Patient and MethodsMicrosatellite stable invasive adenocarcinomas were treated with intravenous Leucovorin 20 mg/m2 and single dose of 5-Flurouracil 400mg/m2 at the time of surgery. High-risk stage II and stage III received the first dose of standard AC at 14 days after surgery. Serial measurements of blood-based biomarkers were measured. Quality of life (QOL) was measured using EORTC QLQ-C30. ResultsOf the 20 patients recruited, 40% had final pathology of stage III, 40% stage II and 20% stage I. All patients received intra-operative chemotherapy with no associated morbidity. Median length of stay was 2 days (range of 2-4). There was no intraoperative morbidity with 5% (N = 1) grade 3 complication. AC was administered to 65% of patients. The median time to AC was 14 days (range 14-36). Overall quality of life and health scores were similar before surgery and at 30-day postoperatively (P < .05). ConclusionsA protocol based on IAC starting at the time of surgical resection was found to be safe and feasible with no adverse effects on surgical morbidity or quality of life. Further prospective studies are needed to explore the oncologic benefit of this novel systemic treatment approach.

Relationship between diverting stoma and adjuvant chemotherapy in patients with rectal cancer: a nationwide study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Patients at risk of recurrence after curative surgery for rectal cancer usually receive adjuvant chemotherapy. Postoperative recovery after low anterior resection (LAR) for rectal cancer can be improved by placement of a diverting stoma to reduce anastomotic leakage. However, it remains unclear how a diverting stoma affects administration of adjuvant chemotherapy in these patients. We identified Japanese patients with rectal cancer who underwent LAR in 2014 and received adjuvant chemotherapy within 12months of surgery in the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Doses of five types of chemotherapy administered (tegafur/uracil, tegafur/gimeracil/oteracil potassium, capecitabine, 5-fluorouracil, and oxaliplatin) were assessed according to the presence or absence of diverting stoma and the timing of stoma closure. There was no significant difference in the cumulative doses of chemotherapy administered in the 12months after LAR between patients with and without diverting stoma, but more doses were administered in the early postoperative period (0-2months after LAR) in patients without diverting stoma. Also, more doses of chemotherapy, regardless of type, were administered in the late closure group (7-12months after LAR) than in the early closure (≤ 6months) and no closure groups. Presence of a diverting stoma did not influence the dose of adjuvant chemotherapy administered within 12months after LAR but could have delayed the start of adjuvant chemotherapy. Patients with late closure of a diverting stoma received more doses of adjuvant chemotherapy administered over 12months.

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis.

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) (5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.

O-4 Average cumulative relative dose of adjuvant chemotherapy is more important than average relative dose intensity for colorectal cancer survival, with implications for treating obese patients: The OCTOPUS consortium

After curative surgery for colorectal cancer (CRC), some studies indicate poorer survival in obese patients. Adjuvant chemotherapy (ACT) for CRC is commonly capped at a body surface area (BSA) ≥2.2m2, potentially reducing chemotherapy average cumulative relative dose (ACRD) and average relative dose intensity (ARDI) in obese patients.

Chemotherapy completion rate for locally advanced rectal cancer at a safety-net hospital.

e15597 Background: Patients with locally advanced rectal cancer (LARC) typically receive chemoradiation prior to surgery, followed by adjuvant chemotherapy (standard). Recently there has been a growing trend toward total neoadjuvant therapy (TNT), in which all chemotherapy is given in the neoadjuvant setting, having the advantage of higher chemotherapy completion rates. Data exploring adherence to both standard therapy and TNT within a vulnerable, underserved population is lacking. Within our safety-net hospital, we determined the chemotherapy completion rates for LARC patients who received TNT vs standard treatment. We also compared two populations within the standard treatment group- those who received all doses of prescribed adjuvant chemotherapy (AC) and those who did not. Methods: A retrospective chart review was performed for all patients with LARC (stage II or III) presenting to Los Angeles County + USC Medical Center from 2015 to 2020. Patients who progressed prior to receiving their first dose of chemotherapy and patients lost to follow-up were excluded. Patient demographics, stage, neoadjuvant/adjuvant treatment, operative characteristics, and postoperative course were abstracted. T-tests and Wilcoxon rank-sum tests were used to compare means and medians, respectively; chi-squared tests were used to compare categorical variables. Results: 67 patients were included- 59 in the standard group and 8 in the TNT group. Mean follow-up was 30 months. All patients in the TNT group completed neoadjuvant chemotherapy. In the standard treatment group, the overall AC completion rate was 81% (n = 48) (Complete Group). 19% (n = 11) did not receive all prescribed doses of AC (Incomplete Group). Compared to patients in the Incomplete Group, patients in the Complete Group were significantly older (mean age 55 vs 48, p = 0.017), had a shorter mean time interval from surgery to initiation of AC (9 weeks vs 13 weeks, p = 0.016), and were less likely to experience a delay in receiving AC &gt; 90 days (15% vs 46%, p = 0.022). In total, 12 patients (20%) in the standard group experienced a delay in AC, of which six (50%) were due to anastomotic leak and/or pelvic abscess. Three of those patients who experienced a delay (25%) required either drain placement or re-operation to address their complication. More patients in the Complete Group went on to have their temporary stomas reversed compared to those in the Incomplete Group (94% vs 70%, p = 0.031). Conclusions: While this population had a high AC completion rate, a meaningful proportion of all patients (though more in the Incomplete Group) experienced a delay in AC &gt; 90 days, with surgical complications responsible for the delay in half of these patients. In contrast, all patients who received TNT completed neoadjuvant chemotherapy. TNT may be a reasonable alternative to reduce therapy delays and further improve chemotherapy completion rates in an underserved population.

Investigation of a Tumor Location-Specific Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.

Objective:An optimal therapeutic strategy for intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein we focused on intrahepatic tumor location and retrospectively analyzed tumor characteristics depending on location to elucidate a location-specific therapeutic strategy for ICC. Methods:Sixty-five ICC patients were divided into three groups based on the distance between the innermost portion of the tumor and portal vein branches observed on preoperative imaging: peripheral, intermediate and central ICC. Results:Median disease-specific survival (DSS) of the peripheral ICC was not reached, whereas median DSS was 32.9 months in intermediate ICC and 25.2 months in central ICC (p <0.05). Vascular invasion was observed in all groups (56-92%). Bile duct invasion to the first branch of the hepatic duct was more commonly observed in central ICC (43%) compared with the peripheral and intermediate ICC (0-8%). Lymph node metastasis was not observed in peripheral ICC, whereas it was frequently observed in intermediate and central ICC (39-44%). A Cox regression analysis revealed sufficient RDI (≥58.3%) of adjuvant chemotherapy (AC) significantly increased the length of DSS (HR: 0.205). Based on these data, we have proposed a location-specific therapeutic strategy as follows: peripheral ICC requires anatomical resection without lymphadenectomy; intermediate ICC requires anatomical resection with lymphadenectomy and sufficient doses of AC; and central ICC requires anatomical resection with extrahepatic bile duct resection, caudate lobectomy, lymphadenectomy, and sufficient doses of AC. Conclusion:We propose an intrahepatic tumor location-specific therapeutic strategy for ICC. This information could contribute to the appropriate therapeutic management of patients with ICC.

Abstract PS13-04: Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database

Abstract Background:In 2017, there are more than 14,000 cases of newly diagnosed breast cancer in Taiwan. With the popularity of early screening policy and social-awareness, the proportion of early breast cancer has increased significantly in the last decades. For the high risk group with early breast cancer, adjuvant systemic chemotherapy could provide lower breast cancer recurrence rate and better overall survival rate. In Taiwan, every citizen must join the National Health Insurance (NIH), and the NIH would cover the whole expanse of adjuvant chemotherapy. Theoretically, all breast cancer patients could receive their condign chemotherapy regardless of their social economic status. The optimal initiation timing of adjuvant chemotherapy is undiscovered, and the effect of delay initiation is still under contestation. In this study, we try to identify the relationship between initiation time of chemotherapy and survival outcome, and different breast cancer subtypes would be analyzed separately. We also evaluate many associated factors that may delay chemotherapy initiation or survival status.Material and Methods:In this observational, populational-based study using Taiwan national breast cancer registry database, we studied 110,784 patients diagnosed with Stage I~III breast cancer between January 1, 2006 and Deccember 31, 2016. Time to chemotherapy(TCC) was defined as the days between surgery and the initial dose of adjuvant chemotherapy. We categorized patients into initiate chemotherapy within 30 days, 31~60 days, 61~90 days, and more than 91 days. The patient demography, tumor biology, lymph node status, type of breast surgery, receiving reconstructive surgery or not, radiation therapy, immunohistochemistry data (estrogen receptor, progesterone receptor, and human epidermal growth factor 2[HER2]), and we categorized patients according to different breast cancer subtypes. Univariate analysis with Kaplan-Meier method is used to evaluate TTC influence, and log-rank test is used to compare differences between groups. Multivariate logistic regression model is used to identify important factors associated with delayed chemotherapy initiation and survival.Preliminary Results:Totally 72840 patients were enrolled in this study, and the median age at initial diagnosis was 52.4 years old. Delayed wound healing and breast reconstruction are the main factors associated with delated TTC. Comparing with TTC&amp;lt;30 days group, TTC of 31~60 days group showed no difference in disease-free survival and overall survival, while TTC of 61~91 days group had a trend of lower disease-free survival (p=0.12). TTC more than 91 days had worse disease-free survival (HR=1.16, 95%CI=1.03~1.38) and overall survival (HR=1.23, 95%CI=1.08~1.52). We assumed initiate first chemotherapy more than 90 days as delated TTC as generally accepted in previous publications. In subgroup analysis, delayed TTC caused worse disease-free survival especially in triple negative group (HR=1.42, 95%CI=1.21~1.68) and HER2 group (HR=1.38, 95%CI=1.22~1.55).Conclusion:For breast cancer patients who assumed to receive adjuvant systemic chemotherapy, delayed in initiation of chemotherapy (more than 90 days) may result in worse outcome, especially in triple negative breast cancer and HER2 group. Besides the above preliminary result, other multivariate analysis and intergroup comparison are still ongoing. More information will reveal in SABCS 2020. Citation Format: Junping Shiau, Fang-Ming Chen, Ming-Feng Hou. Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database [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 PS13-04.

Feasibility and Safety of Perioperative Chemotherapy With Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel for Locally Advanced Gastric Cancer Patients in China.

BackgroundNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).