Completion Of Adjuvant Chemotherapy Research Articles

Using logit panel data modeling to study important factors affecting delayed completion of adjuvant chemotherapy for breast cancer patients

In analysing panel data in which the dependent variable is a binary choice variable taking values 1 or 0 for success or failure respectively, it is feasible to consider the conditional probabilities of the dependent variable. Under strict exogeneity, this conditional probability equals the expected value of the dependent variable. This treatment calls for a nonlinear function which will ensure that the conditional probability lies between 0 and 1, and such functions yield the probit model and the logit model. This paper discusses an estimation of nonlinear logit panel data model with fixed effects. There are two main estimators for such models: 'unconditional maximum likelihood' and 'conditional maximum likelihood'. Application study was designed to determine the most important factors affecting delayed completion of adjuvant chemotherapy among patients with breast cancer and adjuvant chemotherapy improvement outcomes of patients with breast cancer to determine the relationship between time to chemotherapy and outcome according to breast cancer. The optimal timing from beginning to the end of chemotherapy is known (three months). We hypothesized that prolonged time to chemotherapy would be associated with adverse outcomes. Delayed time to chemotherapy was defined as more three months from the first dose and the last dose of chemotherapy. The study results show that the conditional fixed effects logit estimator is efficient and better than the unconditional pooling and unconditional fixed effects logit estimators. And we find that the most important factors affecting delayed completion of adjuvant chemotherapy among patients are haemoglobin, platelets, and alanine transaminase.

Real-world implementation of a geriatric-specific ERAS protocol in patients undergoing colonic cancer surgery

BackgroundThe aim of this single-center observational study was to evaluate the impact of implementing Enhanced Recovery After Surgery (ERAS) protocols, combined with systematic geriatric assessment and support, on surgical and oncological outcomes in patients aged 70 or older undergoing colonic cancer surgery. MethodsTwo groups were formed from an actively maintained database from all patients undergoing laparoscopic colonic surgery for neoplasms during a defined period before (standard group) or after (ERAS group) the introduction of an ERAS program associated with systematic geriatric assessment. The primary outcome was postoperative 90-day morbidity. Secondary outcomes were total length of hospital stay, initiated and completed adjuvant chemotherapy (AC) rate, and 1-year mortality rate. ResultsA total of 266 patients (135 standard and 131 ERAS) were included in the study. Overall 90-day morbidity and mean hospital stay were significantly lower in the ERAS group than in the standard group (22.1% vs. 35.6%, p = 0.02; and 6.2 vs. 9.3 days, p < 0.01, respectively). There were no differences in readmission rates and anastomotic complications. AC was recommended in 114 patients. The rate of initiated treatment was comparable between the groups (66.6% vs. 77.7%, p = 0.69). The rate of completed AC was significantly higher in the ERAS group (50% vs. 20%, p < 0.01) with a lower toxicity rate (57.1% vs. 87.5%, p = 0.002). The 1-year mortality rate was higher in the standard group (7.4% vs. 0.8%, p < 0.01). ConclusionsThe combination of ERAS protocols and geriatric assessment and support reduces the overall morbidity rate and improves 12-month oncologic outcomes.

Experience of treating pediatric hepatoblastoma at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia - Timely surgical intervention playing a key role.

BackgroundMany studies have demonstrated that outcome in patients with hepatoblastoma is determined by tumor resectability and the presence or absence of metastatic disease.PurposeTo evaluate and disseminate information on diagnosis, treatment, and outcome of hepatoblastoma patients at a tertiary care hospital in Saudi Arabia.Patients and methodsTwenty-four pediatric patients with hepatoblastoma were treated at our institution between January 2005 and December 2012. The majority of our patients were stage III and above, while one-third of them presented with metastatic disease. Four (16.7%) had vascular invasion. Two-thirds of our patients (n = 16, 66.7%) had alpha-fetoprotein (AFP) level above 100,000 ng/mL. Twenty-one patients underwent surgery; two had upfront surgery before getting any chemotherapy, and 15 had surgery on schedule after pre-operative chemotherapy. Four patients had delayed surgery as the tumor was not resectable and received extra cycles of chemotherapy. Chemotherapy regimens used were based on SIOPEL study protocols until 2011 and Children’s Oncology Group (COG) protocol from 2012 onwards. Relapse, progressive disease, or death from any cause were defined as events.ResultsFive-year overall survival (OS) of the cohort over a median follow-up time of 56.1 months was 70.6% ± 9.4% with seven (29.2%) events of mortality. No significant difference was found for age at diagnosis (less than 2 years vs. more), stage of disease, AFP levels (less than 100,000 vs. more), vascular invasion, or presence of metastatic disease at presentation in terms of OS. However, children receiving upfront or scheduled as-per-protocol surgery fared better than those who had delayed surgery (as the tumor was not resectable and they received extra cycles of chemotherapy) or did not undergo any surgery (P-Value .001).ConclusionFavorable survival outcome could be achieved with complete tumor excision and adjuvant chemotherapy. Inability to perform surgical excision was the single most important predictor of mortality in our patients.

The influence of age on nutritional status in patients undergoing pancreatic surgery

Rationale: Weight loss and frailty have been associated with a failure to complete adjuvant chemotherapy and poorer prognosis after pancreatic surgery(1,2). We aimed to investigate whether older patients are more likely than younger patients to experience significant weight loss and deterioration in nutritional status following pancreatic surgery.

Obesity and Pancreatic Cancer: A Matched-Pair Survival Analysis.

Background: Morbid obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the impact of obesity on postoperative outcomes and overall survival in patients with PDAC remains a controversial topic. Methods: Patients who underwent pancreatic surgery for PDAC between 1997 and 2018 were included in this study. Matched pairs (1:1) were generated according to age, gender and American Society of Anesthesiologists status. Obesity was defined according to the WHO definition as BMI ≥ 30 kg/m2. The primary endpoint was the difference in overall survival between patients with and without obesity. Results: Out of 553 patients, a total of 76 fully matched pairs were generated. Obese patients had a mean BMI-level of 33 compared to 25 kg/m2 in patients without obesity (p = 0.001). The frequency of arterial hypertension (p = 0.002), intraoperative blood loss (p = 0.039), and perineural invasion (p = 0.033) were also higher in obese patients. Clinically relevant postoperative complications (p = 0.163) and overall survival rates (p = 0.885) were comparable in both study groups. Grade II and III obesity resulted in an impaired overall survival, although this was not statistically significant. Subgroup survival analyses revealed no significant differences for completion of adjuvant chemotherapy and curative-intent surgery. Conclusions: Obesity did not affect overall survival and postoperative complications in these patients with PDAC. Therefore, pancreatic surgery should not be withheld from obese patients.

Postoperative Radiotherapy (PORT) For Patients with pⅢA-N2 EGFR-mutated Non-Small Cell Lung Cancer (NSCLC) after Complete Resection and Adjuvant Chemotherapy

Postoperative Radiotherapy (PORT) For Patients with pⅢA-N2 EGFR-mutated Non-Small Cell Lung Cancer (NSCLC) after Complete Resection and Adjuvant Chemotherapy

Role of complete staging surgery and adjuvant chemotherapy in adults with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery: Experience at a tertiary center in China

Objective: The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma (IMT), is unilateral salpingo-oophorectomy with complete staging surgery (CSS) followed by platinum-based chemotherapy. However, the role of CSS and adjuvant chemotherapy remains controversial.

How Does the Interval Between Completion of Adjuvant Chemotherapy and Initiation of Radiotherapy Impact Clinical Outcomes in Operable Breast Cancer Patients?

PurposeThe aim of this study was to evaluate the impact of time to radiotherapy (TTR) after completion of chemotherapy (CT), and TTR after surgery, in breast cancer (BC) patients.Patients and MethodsContinuous breast cancer patients treated with surgery and CT followed by radiotherapy (RT) from 2009 through 2015 were retrospectively reviewed. Patients were categorized into four groups with respect to TTR after CT, i.e. <4, 4–8, 8–12, and >12 weeks, and TTR after surgery, i.e. <147, 147–180, 180–202, and >202 days. The Cox proportional hazards model was used to identify the independent effect of TTRs.ResultsOverall, 989 patients were enrolled. Patients with a TTR of >12 weeks after CT showed significantly worse breast cancer-specific survival (BCSS) and overall survival (OS) compared with those who had a TTR of <4 weeks (BCSS: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.1–0.76; OS: HR 0.33, 95% CI 0.13–0.88), 4–8 weeks (BCSS: HR 0.23, 95% CI 0.08–0.66; OS: HR 0.29, 95% CI 0.11–0.8), and 8–12 weeks (BCSS: HR 0.22, 95% CI 0.05–0.96; OS: HR 0.23, 95% CI 0.06–0.99). TTR after surgery showed no significant association with survival outcomes in the entire cohort, except in patients with hormone receptor (HR)-positive disease and those receiving mastectomy. In HR-positive tumors, a TTR after CT of >12 weeks remained an independent predictor for adverse BCSS and OS.ConclusionInitiation of RT beyond 12 weeks after CT might compromise survival outcomes. Efforts should be made to avoid delaying RT, especially after completion of CT and in patients with HR-positive tumors, positive lymph nodes, and those receiving mastectomy.

A multi-center, signal-arm study on cancer patients’ perception of chemotherapy side effects, depression, and decision regret at the end of adjuvant treatment

Purpose The aim was to assess patients’ perception of chemotherapy side effects and analyze the relationship between these, depression, and treatment rejection. Methods A multi-center, signal-arm study in 456 patients with resected, non-metastatic cancer. Conducted upon completion of adjuvant chemotherapy. Participants answered questionnaires evaluating chemotherapy side effects (EORTC-QLC-C30), depression (BSI), and decision regret (DRS). Results The three most common symptoms reported by the patients were fatigue (57.5%), insomnia (56.7%), and pain (31%). Only 7.6% (n=35) expressed regret over having opted to receive adjuvant chemotherapy. Fatigue, insomnia, dyspnea, and pain were associated with more depression, while fatigue, pain, and age were associated with decision regret. Conclusion Healthcare professional should consider decreasing fatigue, insomnia, and pain a priority if quality of life is to be improved for patients receiving chemotherapy. The treatment of the side effects of chemotherapy for cancer is essential to improve the quality of life and compliance with the treatment.

Impact of adjuvant chemotherapy or tamoxifen-alone on the ovarian reserve of young women with breast cancer.

To determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on the reproductive potential of women with breast cancer by using a sensitive ovarian reserve marker anti-Mullerian hormone (AMH) as a surrogate. One-hundred-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and Cyclophosphamide-Methotrexate + 5-Fluorouracil (CMF). Longitudinal data were analyzed by mixed effects model for treatment effects over time, adjusting for baseline age and BMI. Both chemotherapy regimens resulted in significant decline in ovarian reserve compared to the tamoxifen-only treatment (p < 0.0001 either regimen vs. tamoxifen for overall trend). AMH levels sharply declined at 12months but did not show a significant recovery from 12 to 18 and 18 to 24months after the completion of AC-based or CMF regimens. The degree of decline did not differ between the two chemotherapy groups (p = 0.53). In contrast, tamoxifen-only treatment did not significantly alter the age-adjusted serum AMH levels over the 24-month follow up. Likewise, the use of adjuvant tamoxifen following AC-based regimens did not affect AMH recovery. Both AC-based regimens and CMF significantly compromise ovarian reserve, without a recovery beyond 12months post-chemotherapy. In contrast, tamoxifen-only treatment does not seem to alter ovarian reserve. These data indicate that the commonly used chemotherapy regimens but not the hormonal therapy compromise future reproductive potential.

Association Among Blood Transfusion, Postoperative Infectious Complications, and Cancer-Specific Survival in Patients with Stage II/III Gastric Cancer After Radical Gastrectomy: Emphasizing Benefit from Adjuvant Chemotherapy

ObjectivesThis study was designed to investigate the potential additive influence of perioperative blood transfusion (BTF) and postoperative infections on cancer-specific survival (CSS) in patients with stage II/III gastric cancer (GC) after radical gastrectomy.MethodsThe medical records of 2114 consecutive stage II/III GC patients who underwent curative resection and planned to receive adjuvant chemotherapy (AC) were retrospectively reviewed. The independent predictive factors for infections were identified using univariate and multivariate analyses. Cox regression analysis was used to assess any associations between BTF, infection and CSS.ResultsA total of 507 (24.0%) received perioperative BTF and 148 (7.0%) developed infections with BTF being identified as an independent predictor for infections. Both BTF and infections independently predicted poor CSS (hazard ratio [HR]: 1.193, 95% confidence interval [CI] 1.007–1.414; HR 1.323, 95% CI 1.013–1.727) and an additive effect was confirmed as patients who had both BTF and infection had even worse CSS. Further stratified analyses showed that complete AC (≥ 6 cycles) could significantly improve CSS in patients who had BTF and/or infection, which was comparable to those without BTF and/or infection (P = 0.496).ConclusionsInfection was the most common complication after gastrectomy and BTF was identified as an independent risk factor. BTF was associated with shorter CSS in stages II/III GC, independent of infections, and receiving BTF and developing infections had an additive effect that was associated with even worse CSS. However, complete AC could significantly improve CSS in these patients. Thus, strategies designed to ensure the completion of AC, such as neoadjuvant chemotherapy, should be further investigated.

Laparoscopic splenectomy for first single-site relapse of ovarian cancer

: Ovarian cancer is an highly aggressive disease and, despite complete surgical cytoreduction and adjuvant chemotherapy, women with this diagnosis usually develop recurrent disease. Platinum-sensitive recurrence can be treated either with secondary cytoreductive surgery (SCS) plus platinum-based chemotherapy or with chemotherapy alone. Patients with isolated splenic metastasis, are relatively rare and could benefit from a minimally invasive approach without compromising survival. In this setting, the advantages of laparoscopy in terms of reduced morbidity, faster recovery, and better cosmetic outcomes are positively reflected on the patient “recurrence experience”, lightening its burden with a potential positive impact on their quality of life. We present the case of a 53-year-old woman with isolated parenchymal splenic recurrence of high-grade serous ovarian cancer that was treated with laparoscopic splenectomy, using an “anterior approach”. Perioperative outcomes of the reported case were superimposable to the open technique, with an estimated blood loss of 50 mL and an operative time of 150 minutes. At 25 months of follow-up, the patient showed no evidence of disease. This study aims to show a step-by-step approach to laparoscopic splenectomy during SCS. In conclusion we showed that, in the hands of an experienced surgeon and through a meticulous surgical technique, laparoscopic splenectomy for recurrent ovarian cancer is feasible and safe.

Abstract CT212: A phase III randomized study of paclitaxel (T) and trastuzumab (H) versus T, H and lapatinib (L) in first line treatment of HER2+ metastatic breast cancer (MBC)

Abstract Background: The addition of H to chemotherapy improved disease outcome in HER2+ MBC. The combination of H and L with chemotherapy improved event free survival (EFS) in the neo-adjuvant setting but not in the adjuvant setting. However, improved EFS did not translate to overall survival benefit. This international trial (ICORG (CTRIAL-IE) 11-10/NCT01526369) compared the efficacy of TH vs. THL in first line treatment of HER2+ MBC. The primary aim of this study was to assess any benefit for the addition of L to TH in an advanced HER2+ breast cancer patient population. Target accrual was not met due to changes to standard of care mid-study. Methods: Patients (Pts) (n= 75 enrolled, randomized 1:1) received weekly T (80mg/m², for 3 weeks of a 4 week cycle) + H (8mg/kg loading dose on cycle 1 day 1 and 4mg/kg every 2 weeks) + L (1,000 mg daily)) until disease progression, unacceptable toxicity or consent withdrawal. The primary outcome measure was progression free survival (PFS). Secondary outcome measure was overall survival (OS). Eligibility criteria included: Female &amp;gt; 18 years, invasive MBC, measurable disease by RECIST criteria V1.1, HER2+ by testing of the primary tumour and if available the biopsied metastatic lesion. No prior systemic therapy for metastatic disease (except one line of hormonal therapy for metastatic disease without H). No recurrence within 12 months (mo) from completion of adjuvant chemotherapy to the development of metastatic disease. No recurrence within 6 mo from completion of adjuvant H to the development of metastatic disease and no prior L treatment. Results: Of the 75 pts enrolled, n=65 (TH n=34, THL n=31) were included in the PFS analysis. Median PFS (95% CI) was numerically higher, but not statistically significant, in THL (24.0 mo (9.5, 34.5)) vs TH (19.3 mo (8.7, 22.7)), HR 0.827, p= 0.601. For OS analysis, n=69 (TH n=35 and THL n=34) were included. 41/69 (59.4%) had no prior therapy. No statistically significant, clinically meaningful improvement in OS (Median (95% CI)) was observed (TH 53.8 mo (41.8, -) vs. THL 45.6 mo (29.7, -), HR 1.048, p=0.891). Analysis of the safety set (n=70 (TH n= 36, THL n=34)) revealed a higher incidence of Grade 3/4 AEs in THL (61.8%) vs. TH (50%), p=0.322. There were 2 on-treatment fatalities due to adverse events (AEs) in the THL arm, one due to respiratory failure, the other due to central nervous system metastasis. There were no on-treatment fatalities in the TH arm. GI disorders were the most prevalent AE, with the incidence of diarrhea significantly higher in the THL arm (88% vs. 42%, p &amp;lt;0.0001). Conclusions: The addition of a HER2-targeted TKI to TH was tolerated with GI toxicity emerging as the predominant AE. While underpowered, this study indicates a numerical advantage in PFS that does not reach statistical significance for the addition of L to TH. This may indicate that the addition of a HER2-targeted TKI to H-containing chemotherapy regimens warrants investigation in HER2+ MBC. Citation Format: John Crown, William Jacot, Denis M. Collins, Linda Coate, Anna Saetersdal, M John Kennedy, Catherine Kelly, Blanca Cantos Sanchez De Ibarguen, Raquel Andrés Conejero, Luis Costa, Margarida Brito, Maccon Keane, Pedro Sanchez Rovira, Miguel Martin, Miriam O'Connor, Manuel Ramos Vazquez, Elena Alvarez, Seamus O'Reilly, Johanna Mattson, Laura Jolis Lopez, Alvaro Rodriguez Lescure, Esperanza Blanco, Coralia Bueno Muino, Brian Moulton, Norma O'Donovan, Andres Hernando, Marc Nolan, Imelda Parker, Giuseppe Gullo, Bryan Hennessy. A phase III randomized study of paclitaxel (T) and trastuzumab (H) versus T, H and lapatinib (L) in first line treatment of HER2+ metastatic breast cancer (MBC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT212.

Current Treatment Considerations for Osteosarcoma Metastatic at Presentation.

Approximately one-fourth of osteosarcoma patients have metastases at presentation. The best treatment options for these patients include chemotherapy, surgery, and radiotherapy; however, the optimal scheme has not yet been defined. Standard chemotherapy for osteosarcoma metastatic at presentation is based on high-dose methotrexate, doxorubicin, and cisplatin (the MAP regimen), with the possible addition of ifosfamide. Surgical treatment continues to be fundamental; complete surgical resection of all sites of disease (primary and metastatic) remains essential for survival. In patients whose tumors do not respond to neoadjuvant chemotherapy, early surgical resection of the primary tumor with limb-salvage surgery or amputation and multiple metastasectomies, if feasible, after the completion of adjuvant chemotherapy is a reasonable option, as the reduction of the tumor volume could probably increase the effect of chemotherapy. Advanced radiotherapy techniques, such as carbon ion radiotherapy and stereotactic radiosurgery, and molecular targeted chemo-therapy with drugs such as pazopanib or apatinib have improved the dismal prognosis, especially for patients who are medically inoperable or who refuse surgery. Given that the presence of metastatic disease at diagnosis of a patient with osteosarcoma is a poor prognostic factor, a multidisciplinary approach by surgeons, medical oncologists, and radiotherapists is important. [Orthopedics. 2020;43(5):e345-e358.].

A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01)

BackgroundAlthough surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial.MethodsThe inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1–28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS).ResultsForty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events.ConclusionsOne-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing.Trial registrationUMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347

Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA.

LBA5 Background: Osimertinib is a 3rd-generation, CNS-active, EGFR-TKI with superior efficacy to comparator EGFR-TKI (gefitinib/erlotinib) in treatment-naïve EGFRm advanced NSCLC. Approx. 30% of pts with NSCLC present with early stage (I–IIIA) disease; surgery is the primary treatment. Adjuvant chemotherapy is standard of care in pts with resected stage II–III NSCLC and select stage IB pts; however, recurrence rates are high and other therapies are needed. ADAURA (NCT02511106) is a Ph III, double-blind, randomized study assessing the efficacy and safety of osimertinib vs placebo (PBO) in pts with stage IB–IIIA EGFRm NSCLC after complete tumor resection and adjuvant chemotherapy, when indicated. Following Independent Data Monitoring Committee recommendation, the trial was unblinded early due to efficacy; we report an unplanned interim analysis. Methods: Eligible pts: ≥18 years (Japan/Taiwan: ≥20), WHO PS 0/1, primary non-squamous stage IB/II/IIIA NSCLC, confirmed EGFRm (ex19del/L858R), complete resection of primary NSCLC with full recovery from surgery; postoperative chemotherapy was allowed. Pts were randomized 1:1 to osimertinib 80 mg once daily orally or PBO to receive treatment for up to 3 years and stratified by stage (IB/II/IIIA), mutation type (ex19del/L858R), and race (Asian/non-Asian). Primary endpoint: disease-free survival (DFS) by investigator in stage II–IIIA pts. Secondary endpoints: overall survival (OS) and safety. Data cutoff (DCO): 17 Jan 2020. Results: Globally, 682 pts were randomized to treatment: osimertinib n=339, PBO n=343. Baseline characteristics were balanced across arms (osimertinib/PBO): stage IB 31/31%, stage II/IIIA 69/69%, female 68/72%, ex19del 55/56%, L858R 45/44%. In stage II–IIIA pts, DFS hazard ratio (HR) was 0.17 (95% CI 0.12, 0.23); p&lt;0.0001 (156/470 events); 2-year DFS rate was 90% with osimertinib vs 44% with PBO. In the overall population, DFS HR was 0.21 (0.16, 0.28); p&lt;0.0001 (196/682 events); 2-year DFS rate was 89% with osimertinib vs 53% with PBO. OS was immature (4% maturity) with 29/682 deaths (osimertinib n=9, PBO n=20) at DCO. The safety profile was consistent with the known safety profile of osimertinib. Conclusions: Adjuvant osimertinib is the 1st targeted agent in a global trial to show a statistically significant and clinically meaningful improvement in DFS in pts with stage IB/II/IIIA EGFRm NSCLC after complete tumor resection and adjuvant chemotherapy, when indicated. Adjuvant osimertinib provides an effective new treatment strategy for these pts. Clinical trial information: NCT02511106 .

PANasta Trial: Cattell Warren versus Blumgart techniques of pancreatico-jejunostomy following pancreato-duodenectomy—A double-blinded multi-centered trial, trial results.

4619 Background: Pancreatic anastomosis failure following pancreatic head excision, for suspected pancreatic cancer, leads to longer recovery and failure to start or complete adjuvant chemotherapy. The aim of this study is to evaluate whether a Blumgart anastomosis (BA) reduces the post operative pancreatic fistula (POPF) rate compared to a more traditional Cattell-Warren anastomosis (CWA). Methods: Patients with suspected pancreatic cancer, undergoing elective pancreato-duodenectomy were randomized intra-operatively to either a BA or a CWA. Anastomoses were constructed according to prior agreed techniques and an operative manual describing key surgical steps. Quality control of these key steps and adherence to the arm of randomization was ensured by operative photographs. Surgical drain amylase was measured post-operatively to establish the primary end point of POPF. These were graded A (biochemical) or B and C (clinically relevant, CR-POPF). Secondary endpoints included: Entry in adjuvant therapy, hospital stay, mortality and survival. Overall survival was estimated using the method of Kaplan Meier and defined as the time from randomisation until death by any cause with alive patients censored at the end of study date. Results: Between May 5 2015 and August 7 2017, 238 patients were randomized, 2 patients withdrew, leaving 236 patients for analysis (112 BA, 124 CWA). Median age was 70 years, 63% were men. Median time from diagnosis to randomization (surgery) was 33 days for both arms. In the BA arm there were 28 POPF’s (15-A, 10-B and 3-C) and 32 in the CWA arm (18-A, 12-B and 2-C), p = 0.887. In total 27 patients (11.4%) developed a CR-POPF, BA 13 (5.5%), CWA 14 (5.9%), p = 0.857. 75% of eligible patients entered chemotherapy, with a median (IQR) time to the start treatment of 2.55 (2.27, 3.15) months for the BA group and 2.87 (2.56, 3.75) for the CWA group. Median hospital stay (IQR) in days was 13 (10-24) for BA and 14.5 (10-22) for CWA, p = 0.232. The overall surgical related mortally at 90 days was 1.7%. 44 study deaths were observed, 35 were due to disease progression (BA 19, CWA 16). A hazard ratio (95% CI) of 0.72 (0.4, 1.311) shows better, but not statistically significant survival for the CWA group. Conclusions: This is the largest surgical trial ever conducted comparing these techniques and there was no significant difference in the POPF rate between the BA and CWA anastomoses. In a UK population the clinically relevant POPF rate is 11% and 75% of eligible patients enter chemotherapy. Clinical trial information: ISRCTN52263879 .

Adjuvant Chemotherapy Use in Patients With Locally Advanced Rectal Cancer: A Single-Institution Experience

BackgroundNational Comprehensive Cancer Network guidelines for the treatment of locally advanced rectal cancer advocate neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy (AC). The aim of this retrospective study was to determine our local patterns of AC use and to examine factors that influenced initiation and completion of AC among patients with stage II/III rectal cancer. Patients and MethodsThe study population consisted of stage II/III rectal cancer patients who were treated at the University of Rochester from 2011 to 2014. Chart reviews were conducted to determine rates of AC initiation and completion. The documented reasons for failure to initiate or complete AC were examined. A multivariate analysis was also completed to evaluate factors that may have influenced the initiation and use of AC. ResultsEighty-one patients were included in the analysis. Median age was 62 years, and 53 (65.4%) were male. Median time from surgery to initiation of AC in those who received AC was 8.0 weeks. Forty-seven patients (58.0%) completed their prescribed AC course. Twenty-four patients (29.6%) did not start AC and 9 patients (11.1%) were unable to complete their course of AC. Primary reasons for not undergoing AC were patient preference (37.5%) and prolonged surgical recovery (33.3%). Primary reasons for not completing AC were treatment toxicities (55.5%) and patient preference (22.2%). Multivariate analysis identified a positive association between clinical stage III disease at diagnosis and initiation of AC. There was no independent association between pathologic response to neoadjuvant therapy at time of surgery and receipt of AC. ConclusionA large proportion of patients at a single academic center did not start or complete their prescribed postoperative AC for locally advanced rectal cancer. Ongoing studies are investigating a total neoadjuvant approach, which may result in better chemotherapy adherence and further improve the pathologic downstaging rate.

Role of staging surgery and adjuvant chemotherapy in adult patients with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery

ObjectiveThe standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging...

P239 Total artificial heart implantation as a bridge to candidacy - an approach to treating primary cardiac sarcoma?

Abstract Background Primary cardiac tumors are rare entities, only 25% of them are malignant. Most common malignant neoplasms of the heart are sarcomas - aggressive tumors with a high rate of local recurrence and systemic metastases. They may lead to a rapid clinical deterioration and sudden circulatory collapse due to obstruction of the intracardiac outflow tract. Most patients affected are younger than 65 years of age. Early diagnosis of cardiac tumors is challenging, echocardiography remains a mainstay of their evaluation. The prognosis is very poor, most patients succumb to disease within months of diagnosis. Complete surgical resection and adjuvant chemotherapy offers palliation and improves survival. Total artificial heart implantation (TAH) allows through, radical resection of large tumors yielding the best possible outcome. Case presentation A 58-year-old male patient with a history of hypertension was admitted to our hospital with a chief complaint of worsening dyspnea and fatigue for last several weeks. Echocardiogram demonstrated a large cardiac mass with abundant vascular supply that incorporated the whole right ventricle and intraventricular septum, extended to the tricuspid valve, infiltrated the left ventricle apex and the base of posterior tricuspid leaflet. The right ventricle cavity was slit-like with small gradient in the outflow track. Cardiac magnetic resonance suggested angiosarcoma or lymphoma. PET-CT did not reveal any extracardiac metastases at that time. The case was discussed at our multidisciplinary cardio-oncology conference. The radical resection of the mass with subsequent TAH implantation was decided upon in high-risk setting, with feasible long-term survival, including eventual consideration for cardiac transplantation (HTX). Native ventricles were excised at the atrioventricular level down to the annulus of the mitral and tricuspid valves. The artificial ventricles were connected to the atrial remnants. The ascending aorta and the main pulmonary artery were dissected close to the valves and connected to outflow grafts. Histopathologic examination of the mass demonstrated angiosarcoma. The patient was started on paklitaksel. After completion of his chemotherapy regimen his eligibility for HTX will be reevaluated. Conclusion Diagnosis and therapy of sarcomas are challenging. Their rarity makes it difficult to standardize therapy. There is few evidence available in literature to guide the treatment of such patients. Case-specific, heart-team-based strategy must be adopted to aid decision making in this rare cases. Sarcomas are lethal, develop rapidly and affect fairly young patients. Prompt surgical resection with subsequent TAH implantation and adjuvant chemotherapy seems ideal in this situation as it offers a possible cure. It gives a slim chance of long-term survival after consecutive HTX for chemotherapy responders. Abstract P239 Figure. Angiosarcoma in TTE, MRI and TEE.