Months Of Chemotherapy Research Articles

Phase II trial of maximal ablative irradiation because of encasement (MAIBE) for patients with potentially resectable locally advanced pancreatic cancer.

710 Background: For patients with localized but not immediately resectable pancreatic adenocarcinoma (PDAC), the role for local therapy remains undefined. Phase II MAIBE trial studied ablative radiation (A-RT) followed by consideration of surgery for patients with locally advanced pancreatic cancer (LAPC) who remain unresectable after induction chemotherapy. Methods: Participants with histologically confirmed PDAC judged unresectable by multidisciplinary review using NCCN definition after completing 3-6 months of mFOLFIRINOX (FFX) or Gemcitabine/Nab-paclitaxel (GN) were eligible. They received hypofractionated A-RT (either 67.5Gy in 15 fractions or 75Gy in 25 fractions based on anatomy) with concurrent capecitabine followed by consideration of resection within 1-3 months. Primary endpoints included resectability (80% power to detect resectability improvement from 15% in historical controls to 30% with α = 0.05) and overall survival (OS) from A-RT. Secondary endpoints included safety of surgical resection after ablative RT using 90-day Clavien-Dindo Classification of adverse events (AE). Results: Between 6/2018 and 4/2022, 47 eligible participants underwent A-RT. Median age was 67 (range, 50-80) years, 24 (51%) were male with a median tumor size of 3.95 (1.6 – 8.3) cm and CA19-9 of 92 ( < 1-1601) U/mL. Forty-four patients (94%) received at least 1 cycle of FFX with a median duration of chemotherapy (FFX or GN) of 3.5 months (1.0 – 9.4). Sixteen (34%) underwent a laparoscopy and 12 (26%) underwent a resection (Pancreaticoduodenectomy, N = 11; distal pancreatectomy, N = 1) at a median time of 3.2 months (1.9-16.9 months) from start of A-RT. The rate of resection satisfied our prespecified boundary of 11. R0 rate was 58.3%. Two-year OS from A-RT for the entire cohort was 38.9% (95% CI, 21.9 – 55.6%), including 37.1% (18.5 - 55.8%) in non-surgical and 39.4% (7.0- 72.1%) in surgical groups. There were no deaths within 90 days of surgery and 9 surgical AEs were recorded in 6 participants, including grade 1 (n = 1), grade 2 (n = 5), grade 3 (n = 2) and grade unknown (n = 1). Conclusions: In patients with LAPC and no metastatic disease after 3-6 months of chemotherapy, A-RT results in a favorable rate of resection without excess surgical toxicity. Promising 2-year OS rates were noted in both resected and non-resected patients. Clinical trial information: NCT03523312 .

A prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma.

163 Background: Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. Methods: A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician’s choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Enrollment of 30 patients was planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size as measured by peritoneal RECIST in observation vs. treatment periods. Results: The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), and 3 were treated with doublet chemotherapy (FOLFOX/FOLFIRI). 15 patients who completed both treatment and observation periods were available for the primary analysis, the mean difference in tumor size was -4.5% (95% CI: -12.6, 3.7), indicating a slight trend towards faster growth on treatment than observation. This difference was not statistically or clinically significant (8.4% growth on treatment vs. 4.0% observation, p=0.26). Of the 18 patients who received any chemotherapy during the study period, zero achieved an objective response, 14 (77.8%) had stable disease during the entire year of follow up, and 4 (12.2%) had progression on study. Patient reported quality of life metrics identified that fatigue (p=0.02), peripheral neuropathy (p=0.014), and financial difficulty (p=0.0013) were all significantly worse while on treatment. There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)). Conclusions: These data from a prospective, randomized crossover trial indicate that patients with low-grade mucinous appendiceal adenocarcinoma do not derive benefit from 5FU based chemotherapy but do incur toxicity. These data further highlight the unique biology of low-grade appendiceal cancer and demonstrates the need to identify novel systemic therapies for this patient population. Clinical trial information: NCT01946854 .

Effectiveness of biologic agents among Hispanics in the US with metastatic colorectal cancer.

16 Background: Randomized clinical trials have demonstrated the survival benefit provided by the addition of biologic drugs to chemotherapy (biochemotherapy) in patients with metastatic colorectal cancer (mCRC). However, Hispanic patients are underrepresented in trial populations with limited data on treatment efficacy in them. We aim to compare effectiveness of chemotherapy vs biochemotherapy among Hispanic population in the US with mCRC. Methods: This study includes two cohorts of patients: 1. age ≥ 65 years mCRC diagnosed from 2004 to 2011 who had received at least 1 dose of chemotherapy and had complete Medicare claims data using the Surveillance, Epidemiology, and End Result (SEER)–Medicare linked database, and 2. local Hispanic population from two hospitals in Bronx, New York, from 2006- 2020. Patient data were classified according to whether they received chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil or capecitabine) or biochemotherapy (bevacizumab, cetuximab, panitumumab, ramucirumab, or aflibercept, started within 3 months of chemotherapy). Overall survival (OS) was defined as the time from starting chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. Results: A total of 188 patients with mCRC were identified. Fifty three (28.2%) received chemotherapy and 135 (71.8%) received biochemotherapy. Median ages were 69 and 68 years, respectively. There were no differences based on median income, marital status, primary site or sidedness, tumor differentiation grades or Charlson Comorbidity Score between both groups. Among patients who received only chemotherapy, 9% received second or greater lines of chemotherapy when compared to 51% in the biochemotherapy group (p <0.001). The median overall survival was 6.6 (95% CI:5.7 - 15.0) months (mo) and 15.9 (12.0 -24.5) mo, respectively. Biochemotherapy conferred an OS benefit with average HR=0.62 (0.41-0.94; p=0.023). This was most evident in the first year (HR=0.53, 0.31-0.89; 0.016), less so in 2nd year (HR=0.65, 0.28 - 1.49; 0.307) and there was an apparent reversal effect beyond 2 years (HR=1.79, 0.41-7.77; 0.436). Conclusions: In this comparative effectiveness study of a cohort of Medicare recipients and the Bronx population, with mCRC, biochemotherapy was associated with an improvement in OS, especially in the 1st year. Patients receiving biochemotherapy are more likely to receive further lines of chemotherapy upon disease progression.

Effect of Different Durations of Adjuvant Capecitabine Monotherapy on the Outcome of High-Risk Stage II and Stage III Colorectal Cancer: A Retrospective Study Based on a CRC Database.

(1) Background: The duration of adjuvant chemotherapy recommended by the NCCN guidelines is 6 months. However, patients are not compliant with intravenous chemotherapy for many reasons; therefore, one approach is to obtain a survival benefit by prolonging the duration of capecitabine monotherapy. (2) Methods: A total of 355 qualified colorectal cancer (CRC) patients from January 2010 to December 2020 at West China Hospital of Sichuan University were selected to receive capecitabine monotherapy for 6−9 months and >12 months. The main endpoints were overall survival (OS) and disease-free survival (DFS). (3) Results: Among stage III patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 80.7%% and 66.8%, respectively, and the 5-year OS rates were 94.7%% and 88.8%, respectively. Among high-risk stage II patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 81.5% and 78.6%, respectively, and the 5-year OS rates were 93.1% and 84.2%, respectively. (4) Conclusions: Twelve months of chemotherapy demonstrated superior OS and DFS to that of six months in the stage III group but showed no difference in the high-risk stage II group. The better OS and DFS observed in the 12-month treatment period could be of value in selected cases.

Clinicopathological and Prognostic Values of Telomerase Reverse Transcriptase (TERT) Promoter Mutations in Ovarian Clear Cell Carcinoma for Predicting Tumor Recurrence, Platinum Resistance and Survival.

A small subset of patients with ovarian clear cell carcinoma (OCCC) harbors telomerase reverse transcriptase promoter (TERTp) mutations. We aimed to analyze the clinicopathological and molecular characteristics of TERTp-mutant OCCC and investigate whether TERTp mutations are associated with the clinicopathological characteristics and outcomes of patients with OCCC. We included 11 OCCC cases in our study. Targeted sequencing was performed with a thorough review of pathology slides and electronic medical records. Eleven OCCCs harbored two hotspot TERTp mutations: c.1-146C>T (6/11) and c.1-124C>T (5/11). All patients (11/11) who underwent postoperative adjuvant chemotherapy experienced tumor recurrence, and eight of them were classified as platinum-resistant. TERTp-mutant OCCC showed significantly higher frequencies of postoperative recurrence and relapse within six months of chemotherapy. TERTp mutations significantly predicted disease-free survival (DFS) in patients with OCCC. We demonstrate that TERTp mutations have significant prognostic value for predicting tumor recurrence, platinum resistance, and worse DFS in patients with OCCC.

Non-Hodgkin’s Lymphoma Presenting Section as a Soft Tissue Mass on Right Thigh

Non-Hodgkin’s Lymphomas (NHL) are a heterogeneous group of lymphoproliferative malignancies with a greater preference for disseminating to extranodal locations. Prevalence of extranodal involvement in NHL has increased in the past decade, and the sites involved are the stomach, spleen, waldeyer’s ring, Central Nervous System (CNS), lungs and skin. This is a rare case of NHL in a 48-year-old female who presented with solitary exophytic mass with ulceration over the right thigh and erythematous plaque over postaxillary region and enlarged right inguinal and left axillary lymph nodes. Magnetic Resonance Imaging (MRI) of the right thigh showed lobulated mass involving skin and subcutaneous soft tissues without any intramuscular extension suggestive of neoplastic mass. Fine needle aspiration cytology of the inguinal node and biopsy of the right thigh lesion showed features suggestive of NHL. She was treated with three cycles of Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisone (CHOP) regimen, but the patient succumbed to death after six months of chemotherapy

Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Chemotherapy Induced Eosinophilia and its Significance among the Cancer Patients Treated at a Tertiary Care Teaching Hospital, West Bengal

AbstractBackground: Cancer is a major burden and threat to global society. It is one of the leading causes of death inboth developed and developing countries. The main modalities used for its treatment include surgery, radiation,chemotherapy, immunotherapy, and hormones.Materials & Methods: The current study was performed to find incidence of chemotherapy induced eosinopilliain patients with different cancers who were receiving standard chemotherapy regimens (minimum two cycles andmaximum six to eight cycles). Total leucocyte count, absolute eosinophil count and differential leucocyte countwas done just before starting of chemotherapy. Differential leucocyte count (DLC) was reported after 1st cycle ofchemotherapy agents, before last dose of chemotherapy, after 6 weeks of completion of chemotherapy, and aftersix month of completion of chemotherapy to see the changes on eosinophil counts.Results: Most commonly used anticancer agents were 5 FU 61 (61%), doxorubicin 43 (43%), cyclophosphomide 53(53%), cisplatin 10 (10%), paclitaxel 20 (20%), carboplatin 25 (25%), gemcitabine 11 (11%), oxaliplatin 14 (14%) andcapecitabine 11 (11%). The pre-CT eosinophil count had a mean of 3.41 (range, 2 to 4) and post-CT after 1st dosehad a mean of 5.06 (range, 3 to 8) (p <0.0001). The pre-CT eosinophil count had a mean of 3.41 (range, 2 to 4) andpost-CT after 6 months of chemotherapy had a mean of 6.85 (range, 5 to 8) (p <0.0001). Increased eosinophil countafter 1st dose and 6 months completion of chemotherapy was highly significant from baseline values (P < 0.0001).Conclusion: Study has generated a hypothesis that administration of many anticancer agents may increaseeosinophil count or peripheral eosinophilia. Additional large scale prospective studies must be performed toconfirm our results.

Chemotherapy-Induced Peripheral Neuropathy Leading to Foot Deformity

A 14-year-old boy was diagnosed with mixed phenotype acute leukemia and underwent 28 months of chemotherapy with vincristine and methotrexate. Early in his chemotherapy treatment, he developed hyperalgesia of his feet and ankles, particularly on the left side, believed to be due to the vincristine. Despite medical treatment, he continued to have hyperalgesia and increasing left foot deformity and pain that markedly affected his walking. He presented for orthopaedic evaluation at the end of his chemotherapy and had foot deformities that were corrected surgically with substantial improvement in his foot position and walking ability. He remains in remission for his leukemia. The effects of chemotherapy-induced peripheral neuropathy on the lower extremities are reviewed.

Association Between Race and Irritability, Inflammation, and Depression During Chemotherapy

Objectives: This study aimed to assess whether race modifies irritability and immunological inflammation, and their interaction to worsen depression during chemotherapy. Methods: 25 African American and 19 White nonmetastasized breast cancer patients were assessed on irritability, inflammation biomarker (hsCRP and IL-6), and depression at baseline (T 1 ) and after 3 months of chemotherapy (T 2 ). Wilcoxon rank sum test was performed to compare racial groups on these study variables. Generalized estimating equations (GEE) regression models for repeated measures were computed, using the severity of depression as the dependent variable, race, an inflammation biomarker (hsCRP or IL-6), irritability, interactions of these variables, and time as independent variables, controlling for age, baseline depression severity level and its racial difference. Results: The African American cancer patients had significantly higher levels of hsCRP (p = .040) and IL-6 (p = .018) than the White patients at T 2, without a significant baseline difference. In both regression models, the African American patients experiencing greater irritability reported significantly more severe depression at T 2 (p = .0002; .0048). In the regression model containing hsCRP, a negative interaction between irritability and hsCRP level was significantly associated with more severe depression at T 2 (p < .0001). In the regression model containing IL- 6, the African American patients (p = .03), most of whom had higher IL-6 (p < .0001), reported significantly more severe depression at T 2 , while White patients who had higher IL-6 levels also had more severe depression at T 2 (p = .016). Conclusion: Association between irritability and depression was significantly stronger for the African American patients than the White patients in this study, and the level of hsCRP influenced irritability and its association with depression. Identification of contributors to irritability, particularly for African Americans, is important for reducing irritability and depression in cancer patients undergoing chemotherapy. Moreover, the White cancer patients in the study who experienced higher IL-6 levels during chemotherapy were also at a higher risk of worsening depression and required medical attention.

Clinical effectiveness of bedaquilin and delamanid treatment of children and adolescents with drug-­resistant tuberculosis

Objective — to study the clinical effectiveness of chemotherapy using bedaquiline (Bdq) and delamanid (Dlm) in children and adolescents with multidrug-resistant (MDR) and extensive drug resistant (XDR) pulmonary tuberculosis of lungs (TBL).
 Materials and methods. A retrospective cohort analysis of the medical records of 40 patients with pulmonary tuberculosis (TB) with MDR/XDR was conducted in order to study the clinical effectiveness of chemotherapy with Bdq and Dlm. Among 40 patients were 25 (62.5 %) children aged 0 to 14 years and 15 (37.5 %) — teenagers aged 15 to 17; there were 18 (47.5 %) boys, 22 (52.5 %) girls. The patients were divided into two groups: the first group — 25 children and the second group — 15 teenagers. Microbiological research in children and adolescents included: detection of Mycobacterium tuberculosis (MTB) in sputum by smear microscopy, sowing of material on Levenstein—Jensen medium, typing of isolated mycobacteria on BACTEC MGIT 960, determination of the drug susceptibility test of strains of MTB to antituberculosis drugs (ATBDs) of first- and second-line, as well as molecular genetic research of sputum, in particular by GeneXpert MTB/RIF/Ultra and linear probe analysis. All children and adolescents received an individualized treatment regimen depending on the resistance of MTB to ATBDs or on the resistance of MTB at the source of infection.
 Results and discussion. Among the examined children (25), who were prescribed Bdq and Dlm, almost half (44.0 %) were aged from 0 to 4 years, 12.0 % — from 5 to 8 years and 44.0 % — from 9 to 14 years. Patients aged 17 years (46.7 %) prevailed among teenagers (15). MDR/RIF-TB was diagnosed in 10 (40.0%), XDR-TB determined in 3 (12.0 %) and risk of MDR-TB (RMDR-TB) — in 12 (48.0 %) children who were prescribed a new treatment regimen with Bdq and Dlm. At the same time, MDR-TB diagnosed 1.7 times more often, XDR-TB 2.8 times more often and RMDR-TB 3.3 times less often among adolescents compared to children.The primary tuberculous complex found in 12 (48.0 %) children, TB damage of lung and bone — in 4 (16.0 %), TB of the intrathoracic lymph nodes — in 3 (12.0 %), TB of the lungs and central nervous system — in 2 (8.0 %) and infiltrative TB of the lungs — in 3 (12.0 %). The infiltrative pulmonary TB was observed 7.5 times more often and the disseminated form 3.3 times more often in adolescents than in children.All children didn’t excretion of MTB after the two months of treatment with Bdq and Dlm. However, non-bacterial excretion in all adolescents was achieved within 3 months of chemotherapy (CT). Significant positive X-ray dynamics were found in 23 (92.0 %) children and 12 (80.0 %) adolescents during 9 months of CT. Lung changes remained in 2 (8.0 %) children and 3 (20.0 %) adolescents after 9 months of treatment. However, in both children and adolescents resolution of infiltration, densification of focies and formation of fibrosis in the lungs were confirmed radiologically at the end of the course of treatment.
 Conclusions. Among 21 (84.0%) children and 10 (66.7 %) adolescents were cured at the end of the course of complex treatment with the use of Bdq and Dlm. Treatment was completed 2 times more often in adolescents than in children (33.3 vs. 16.0 %, p < 0.05). The success of the treatment at the occurrence of new ATBDs was established in all children and adolescents. In addition, among 84.0 % children and 73.3 % adolescents the treatment ended with the formation of small residual changes.

Physical Activity Program for the Survival of Elderly Patients With Lymphoma: Study Protocol for Randomized Phase 3 Trial.

The practice of regular physical activity can reduce the incidence of certain cancers (colon, breast, and prostate) and improve overall survival after treatment by reducing fatigue and the risk of relapse. This impact on survival has only been demonstrated in active patients with lymphoma before and after treatment. As poor general health status reduces the chances of survival and these patients are most likely to also have sarcopenia, it is important to be able to improve their physical function through adapted physical activity (APA) as part of supportive care management. Unfortunately, APA is often saved for patients with advanced blood cancer. As a result, there is a lack of data regarding the impact of standardized regular practice of APA and concomitant chemotherapy as first-line treatment on lymphoma survival. This study aimed to assess the impact of a new and open rehabilitation program suitable for a frail population of patients treated for diffuse large B-cell lymphoma (DLBCL). PHARAOM (Physical Activity Program for the Survival of Elderly Patients with Lymphoma) is a phase 3 randomized (1:1) study focusing on a frail population of patients treated for DLBCL. The study will include 186 older adult patients with DLBCL (aged >65 years) receiving rituximab and chemotherapy. Overall, 50% (93/186) of patients (investigational group) will receive APA along with chemotherapy, and they will be supervised by a dedicated qualified kinesiologist. The APA program will include endurance and resistance training at moderate intensity 3 times a week during the 6 months of chemotherapy. The primary end point of this study will be event-free survival of the patients. The secondary end points will include the overall survival, progression-free survival, prevalence of sarcopenia and undernutrition, and patients' quality of life. This study will be conducted in accordance with the principles of the Declaration of Helsinki. Recruitment, enrollment, and data collection began in February 2021, and 4 participants have been enrolled in the study as of July 2022. Data analysis will begin after the completion of data collection. Future outcomes will be published in peer-reviewed health-related research journals and presented at national congress, and state professional meetings. This publication is based on protocol version 1.1, August 3, 2020. The PHARAOM study focuses on highlighting the benefits of APA intervention on survival during the period of first-line treatment of patients with DLBCL. This study could also contribute to our understanding of how an APA program can reduce complications such as sarcopenia in patients with lymphoma and improve their quality of life. By documenting the prevalence and relationship between sarcopenia and exercise load, we might be able to help physicians plan better interventions in the care of patients with DLBCL. ClinicalTrials.gov NCT04670029; https://clinicaltrials.gov/ct2/show/NCT04670029. DERR1-10.2196/40969.

Stereotactic MR-Guided On-Table Adaptive Radiation Therapy (SMART) for Patients with Borderline or Locally Advanced Pancreatic Cancer: Primary Endpoint Outcomes of a Prospective Phase II Multi-Center International Trial

<h3>Purpose/Objective(s)</h3> Retrospective studies demonstrate that ablative stereotactic MR-guided on-table adaptive radiation therapy (SMART) achieves favorable local control (LC) and overall survival (OS) with limited grade 3+ toxicity compared to historical non-ablative outcomes for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC). We conducted an international multi-center single-arm phase 2 trial of ablative 5-fraction SMART for LAPC/BRPC. <h3>Materials/Methods</h3> Subjectswere required to have biopsy-confirmed adenocarcinoma, receive ≥3 months of chemotherapy, have no distant metastasis and CA19-9 ≤500 U/mL. SMART was delivered on a 0.35T MR-⁶⁰Co or MR-linac system prescribed to 50 Gy in 5 fractions (biologically effective dose₁₀ [BED₁₀]=100 Gy) using continuous intrafraction cine-MRI, soft tissue tracking, and automatic beam gating. The original plan was recomputed onto the daily anatomy and if that plan would not have met constraints, on-table adaptive replanning using an isotoxicity approach was performed. The primary objective was to demonstrate <15.8% acute grade 3+ gastrointestinal (GI) toxicity definitely related to SMART measured through 90 days and evaluated according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE). All patients have completed 90-day follow-up. Secondary objectives included OS, distant progression free survival (DPFS), and patient-reported quality of life. <h3>Results</h3> 136 patients across 13 sites were enrolled between 2019-2021. Mean age was 65.7 years. Head of pancreas lesions were most common (66.9%; n=91). 43.4% (n=59) had BRPC, 56.6% (n=77) LAPC. Mean induction chemotherapy duration was 155.7 days, typically with FOLFIRINOX 65.4% (n=89) or gemcitabine doublet 16.9% (n=23). Mean CA19-9 after induction chemotherapy was 71.7 U/mL. On-table adaptive replanning was used for 93.1% of fractions. SMART was delivered in consecutive days (56.6%) or every other day (43.4%). Median follow-up was 16.4 months and 8.8 months from diagnosis and SMART, respectively. 31.6% (n=43) had surgery after SMART. The incidence of acute grade 3+ GI toxicity definitely and probably related to SMART were 0% and 2.2% (n=3), respectively. 1-year LC and DPFS from SMART were 82.9% and 50.6%, respectively. 1-year OS was 93.9% from diagnosis and 65.0% from SMART. <h3>Conclusion</h3> This is the first prospective, multi-institutional study of ablative SMART with prescribed BED₁₀ of 100 Gy delivered in 5 fractions for BRPC/LAPC. The primary objective was met, signaling that further prospective evaluation of ablative SMART for BRPC/LAPC is warranted with a focus on long-term LC and OS compared to chemotherapy alone.

Trial in Progress: 2019-1001 A Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma (LAPC or BRPC)

<h3>Purpose/Objective(s)</h3> Patients with pancreatic ductal adenocarcinoma (PDAC), who are not eligible for surgery after induction chemotherapy often receive radiation. Although radiation therapy (RT) improves local disease control, the placement of the pancreas proves to be difficult when safely delivering therapeutic doses. NBTXR3 is a novel, potentially first-in-class radio enhancer, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by RT. Pre-clinical testing suggests up to a 9-fold enhancement of the RT dose delivered within tumor cells. In this phase 1 trial-in-progress, the primary objective is to determine the recommended phase II dose (RP2D) of NBTXR3 for LAPC and BRPC patients undergoing RT. The secondary objectives are to evaluate the safety, feasibility, and anti-tumor response of NBTXR3 intratumoral injection on PDAC patients as well as time-to-event outcomes of subjects. <h3>Materials/Methods</h3> For the dose-finding part 1 of the study, patients with LAPC and no metastatic disease after at least 2-6 months of chemotherapy will be eligible. For part 2, the expansion at RP2D, patients with BRPC or LAPC and no metastatic disease after chemotherapy will be eligible. The statistical design of the trial uses a Bayesian optimal interval (BOIN) design. A maximum of 24 patients will be enrolled. For baseline and follow-up, imaging and blood biomarkers will be collected. Patients enrolled will receive NBTXR3, once, through intratumoral injection via endoscopic ultrasound (Day 1). Pre-treatment biopsy will be collected. Post NBTXR3 injection, blood samples will be collected at 4 time points (0,5,30, and 120 minutes). Two urine voids will be collected post injection for hafnium quantification as well. At least three days later, patients will undergo imaging for RT dosimetry and planning where NBTXR3 can be visualized. Patients will then receive 45 Gy in 15 fractions with IMRT, with regional nodal basins receiving 37.5 Gy. Follow-up period will begin 4 weeks after end of treatment and continue every 3 months for a year. Patients will be evaluated for surgery 4-12 weeks post RT. At 11-13 weeks after end of RT, if the patient is not eligible for surgery, an endoscopic ultrasound procedure will be performed. In both events, a post-treatment biopsy will be obtained. The imaging collected of pancreatic target lesion will be used to determine tumor response as per RECIST v1.1 criteria. <h3>Results</h3> Trial is open and accruing, with 8 patients enrolled so far. <h3>Conclusion</h3> We expect to determine the RP2D, safety, and preliminary efficacy of NBTXR3 in pancreatic cancer with this study with blood, tissue, and imaging correlates in 2022.

Association of clinic type with receipt of neoadjuvant therapy among patients with localized pancreatic cancer: Value of multidisciplinary clinic.

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.

Sequential Geriatric Assessment in Older Patients with Colorectal Cancer during Chemotherapy: Subgroup Analysis of a Prospective, Multicenter Study EpiReal 75

Introduction: Colorectal cancer (CRC) is a disease of older patients, but evidence-based guidelines for chemotherapy in older patients are scarce. Geriatric assessment (GA) evaluates a patient’s functional status (FS) and helps in decision-making when choosing chemotherapy for older patients. However, the change of FS during chemotherapy is rarely studied as GA is mostly performed once instead of sequentially. Methods: We performed a subgroup analysis of a prospective, multicenter study EpiReal 75. Patients aged ≥75 years with gastrointestinal malignancy prior to initiation of chemotherapy or receiving palliative chemotherapy were screened. We defined geriatric core assessments including the Eastern Cooperative Oncology Group score, Barthel’s activities of daily living (ADL) scale, Lawton’s instrumental activities of daily living (IADL) scale, and G-8 questionnaire, which were performed at baseline and repeated every 3 months. Quality of life (QoL) assessed by QLQ-C30 questionnaire was also re-evaluated every 3 months. We defined any deterioration in any of the geriatric parameters as unstable in the corresponding function. Results: 28 patients with CRC were enrolled between April 2014 and December 2018. 20 patients were evaluable for statistical analysis with a mean age of 78.5 years (range, 75–88). Most patients received chemotherapy in palliative setting. During 3 months of chemotherapy, 25% of patients became more dependent as measured by ADL or IADL. During a median follow-up of 15 months, patients with unstable ADL or IADL had a significantly shorter overall survival (OS) than those with stable ADL or IADL (p_logrank = 0.0055 and 0.0253, respectively), without a significant difference in progression-free survival (PFS). Also, unstable IADL correlated with a deterioration in aspects of QoL such as role functioning and emotional functioning (p = 0.0189 and 0.0239, respectively). 20% of patients experienced treatment-related grade 3 adverse events (AEs), no grade 4–5 AEs occurred. Conclusion: Sequential GA revealed changes in FS in older patients with CRC receiving chemotherapy. A deterioration of FS during chemotherapy did not influence PFS but had a negative impact on OS and QoL. It is therefore important to maintain FS in older patients with cancer, and regular performance of geriatric core assessments should be encouraged in the clinical practice.

Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study

BackgroundAlthough pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the skeleton, disseminated tumor cells have been detected in bone marrow samples from patients with this disease. The prognostic value of such findings is currently unclear. Thus, the current study aimed to clarify the prognostic information associated with disseminated tumor cell detection in samples from patients with PDAC.MethodsBone marrow aspirates were obtained from 48 patients with locally advanced (n = 11) or metastatic (n = 37) PDAC, before and after 2 months of chemotherapy. Disseminated tumor cells were detected with an mRNA panel and quantitative reverse transcription PCR. We used the highest levels measured in healthy bone marrow (n = 30) as a threshold to define the positive detection of disseminated tumor cells. Progression-free and overall survival were analyzed with Kaplan–Meier and Cox proportional hazards regression analyses.ResultsDisseminated tumor cells were detected in 15/48 (31%) bone marrow samples obtained before starting chemotherapy and in 8/25 (32%) samples obtained during chemotherapy. Patients with disseminated tumor cells detected before therapy had significantly shorter progression-free (p = 0.03; HR = 2.0) and overall survival (p = 0.03; HR = 2.0), compared to those without disseminated tumor cells in the bone marrow. When restricting disseminated tumor cell detection to keratins KRT7 and KRT8, the prognostic information was substantially stronger (p = 1 × 10–6; HR = 22, and p = 2 × 10–5; HR = 7.7, respectively). The multivariable Cox regression analysis demonstrated that disseminated tumor cell detection prior to treatment had independent prognostic value. In contrast, disseminated tumor cells detected during treatment did not have prognostic value.ConclusionsDisseminated tumor cells detected before commencing chemotherapy had prognostic value in patients with inoperable PDAC.

The impact of vertical integration of oncologists on cancer outcomes and healthcare costs among metastatic prostate cancer patients.

e18786 Background: The share of oncology practices that were vertically integrated with hospitals more than doubled in the past decade. Vertical integration leads to higher spending, but evidence on quality and outcomes remains inconclusive. This study examines how integration between hospitals and oncologists affects patient outcomes and spending among patients with metastatic prostate cancer. Methods: Using the SEER-Medicare linkage with the Medicare Data on Provider Practice and Specialty file, we identified Medicare beneficiaries diagnosed with metastatic, castration-resistant prostate cancer who initiated chemotherapy between 2008-2017 (n = 9,167). We used a claims-based approach to identify treating oncologists and their integration status (as indexed by percent of total services billed to hospital outpatient departments). Outcomes included: 1) time on chemotherapy, 2) survival from chemotherapy initiation, 3) supportive care use (i.e. bone-modifying agents [BMA]), 4) Medicare payment for the first 3 months of chemotherapy initiation and last 3 months before end of life (EOL). The differences-in-differences approach was used to compare patient outcomes before and after oncologists became integrated versus those whose oncologists remained non-integrated or always integrated. Weibull survival and linear models were used for regression analysis, adjusting for sociodemographic, clinical, and market characteristics. Results: The proportion of patients treated by integrated oncologists increased from 28% in 2008 to 55% in 2017. Vertical integration was associated with 13.6 percentage points increase (95% CI = 6.1 to 21.1) in the likelihood of BMA use, but no significant changes for time on chemotherapy and survival. Average Medicare spending in the first 3 months of chemotherapy initiation and last 3 months of EOL was $34,324 and $42,624, respectively. Vertical integration did not have a significant effect on overall spending. Further decomposition showed decreases in professional service costs (-$4,264, 95% CI = -$6,642 to -$1,887) along with an increase in outpatient care costs ($3,941, 95% CI = $159 to $7,723) for the first 3 months of chemotherapy. A similar pattern was found for spending in the last 3 months of EOL. Conclusions: Vertical integration of oncologists was associated with increased use of supportive care, but not time on chemotherapy or survival among metastatic prostate cancer patients. Although oncologists switched service billing from physician offices to hospital outpatient departments, we did not detect significant increases in total Medicare spending after vertical integration. This suggests the potential for quality improvement following vertical integration without substantial increases in healthcare spending. Future studies should extend the investigation to other cancer types and patient outcomes.

Impact of cardiometabolic health and abdominal adipose tissue on physical function in women with breast cancer (WF-97415).

e18696 Background: Breast cancer treatments often result in a decline in physical function that may be worsened by high levels of abdominal adipose tissue (AAT). However, the role of cardiometabolic health, which is comprised of interrelated risk factors of insulin resistance, dyslipidemia, hypertension, and central adiposity, has been infrequently addressed. Thus, we evaluated the relationship between physical function and cardiometabolic health controlling for AAT in women with breast cancer before and during receipt of potentially cardiotoxic chemotherapy. Methods: Women recruited through NCORP with stage I-III breast cancer completed a six-minute walk distance (6MWD) test to determine physical function, magnetic resonance imaging (MRI) to evaluate AAT, and assessments of cardiometabolic health before and following 3 months of chemotherapy. Specifically, MRI was used to measure waist circumference (WC), and AAT components of subcutaneous (SAT) and visceral adipose tissue (VAT). To assess cardiometabolic health, individual metabolic syndrome (MetS) components of WC, mean arterial pressure (MAP), glucose (FPG), high-density lipoprotein cholesterol (HDL), and triglycerides (TG) were used to calculate a MetS severity z-score (MetS-Z) = [(WC-88)/SD] + [(MAP-100)/SD] + [(FPG-100)/SD] + [(50-HDL)/SD] + [(TG-150)/SD]. All measures were assessed by individuals blinded to visit, demographic data, and other components of the study. Baseline and 3-month data were compared via paired t-tests. Regression analyses were used to identify the relationship between 6MWD and MetS-Z and possible mediation effects of AAT (i.e., SAT and VAT). Results: One hundred eleven women with a mean age of 56.1 ± 11.0 yrs completed assessments. After 3 months of chemotherapy, 6MWD was lower (457 ± 90.7 vs 428 ± 92.9 m, P= 0.001) and MetS-Z was increased (-1.13 ± 3.01 vs 0.30 ± 3.97 AU, P&lt; 0.001) compared to baseline. The increase in MetS-Z was mainly attributed to elevations in TG (120 ± 81 vs 154 ± 111 mg/dl, P&lt; 0.001) and decreases in HDL (58.6 ± 14.3 vs 47.7 ± 13.9 mg/dl, P&lt; 0.001). No changes were observed in SAT ( P= 0.15) or VAT ( P= 0.42). Although MetS-Z was associated with 6MWD at baseline ( P= 0.01), MetS-Z was not significant predictor after controlling for SAT and VAT (B = -3.39, P= 0.34, 95% CI [-10.4, 3.62]). MetS-Z also associated wtih 6MWD at 3 months ( P= 0.002) and this remained significant after controlling for SAT and VAT (B = -5.36, P= 0.03, 95% CI [-10.3, -0.46]). Conclusions: AAT may be more strongly associated with physical function prior to chemotherapy whereas cardiometabolic traits may have clinical implications during treatment in women with breast cancer. Additional longitudinal work investigating the effects of concurrent treatments (e.g., exercise, diet, pharmacological) on the relationship between cardiometabolic health and physical function is warranted. Clinical trial information: NCT02791581.

P-247 Outcomes of randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma

Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). The rarity of appendiceal adenocarcinoma has made it difficult to study with traditional prospective, randomized controlled trials. As a result, current national guidelines still suggest that appendiceal cancer be treated similarly to colorectal cancer (CRC) despite clear differences between the two in terms of both clinical and molecular features. While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician’s choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Up to 30 patients were planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size in observation vs. treatment periods. Patients were monitored for rate of bowel complications as a secondary endpoint for the study. The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), one patient was treated with FOLFOX, 2 (8%) were treated with FOLFIRI. Four patients did not get any chemotherapy (17%). There were 15 patients available for the primary analysis of change in tumor volume as measured by modified peritoneal RECIST. The mean difference in tumor size was -4.5 (95% CI: -12.6, 3.7), indicating a trend towards faster growth on treatment than observation, however there was no significant difference in growth of tumor during observation vs. treatment time periods (8.4% growth treatment vs. 4.0% observation, p=0.26). Separately we combined all patients with available 6- or 12-month information regardless of treatment order accounting for repeated measures again finding no significant difference (13.1% vs. 4.4%, p=0.14, n=18). There was no significant difference in overall survival between treatment first or observation first arms (76 vs. 42 months, p = 0.37). There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)), and no bowel perforations occurred on study. These data from a prospective, randomized crossover design trial suggest that patients with low-grade mucinous appendiceal adenocarcinoma do not appear to derive benefit from 5FU based chemotherapy. These data further highlight the unique biology of low-grade mucinous appendiceal adenocarcinomas and demonstrates the need to identify effective systemic therapies for this patient population.