Adjuvant Treatment Regimens Research Articles

Does adjuvant chemoradiation benefit patients with lymph node-positive biliary tract cancer? A secondary analysis of SWOG S0809.

4104 Background: Biliary tract cancers are rare tumors with a median overall survival (OS) of 16 months for node-positive (N+) and 37 months for node-negative (N0) disease despite resection. Lymph node status is a known strong prognostic factor for local recurrence with an average estimated 2-year disease-free survival (DFS): 65.5% for N0 and 29.7% for N+ tumors. The Phase II Intergroup Trial S0809 showed that adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine improved OS in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBC) compared to historical controls. We hypothesized that nodal status is a prognostic factor for local recurrence in this patient population who received adjuvant therapy. Methods: This analysis included patients with stage pT2-4, N+ or positive margin EHCC or GBC. Treatment included four cycles of gemcitabine (1,000 mg/m2 intravenously on days 1 and 8) and capecitabine (1,500 mg/m2 per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m2 per day) and radiotherapy (45 Gy to regional lymphatics; 52.5 to 59.4 Gy to tumor bed). S0809 patients who did not receive radiotherapy were excluded from analysis. Correlations between nodal status, resection margin, and other clinicopathological factors, patterns of recurrence and survival were analyzed, and Cox regression models were used to estimate the prognostic significance of nodal status. A Z-test was used to compare DFS rates between these patients and historical data. Results: A total of 69 patients [EHCC n = 46 (66%); GBCA n = 23 (33%)] were evaluated with a median age of 61.7 (26.1-80.6). The majority of N0 patients were female (17/24, 70.8%), whereas most N+ patients were male (25/45, 55.6%; p < 0.04). Distribution of R0 (66.7%) and R1 (33.3%) resections was similar in the N0 and N+ groups. Thirty-four patients with EHCC had N+ disease (73.9%) compared with 11 patients with GBCA (47.8%, p = 0.03). Nodal status did not significantly impact OS (HR = 2.03, 95% CI 0.92-4.49, p = 0.08) or DFS (HR = 1.75, 95% CI 0.85-3.59, p = 0.13). Two-year OS was 70.6% for N0 and 60.9% for N+ disease (p = 0.11). Nodal status was not significantly associated with 2-year DFS: 62.5% for N0 and 49.8% for N+ (p = 0.20). N+ vs N0 tumors showed higher rates of distant failure (51.1% vs 25.0%, p < 0.04), but similar local recurrence (17.8% vs 12.5%, p = 0.88). The observed 2-year DFS in patients with N+ tumors was significantly longer compared to the historical rate of 29.7% (p = 0.004). Conclusions: This combination adjuvant treatment regimen following curative resection for EHCC and GBCA provides favorable outcomes regardless of nodal status. These data suggest that adjuvant chemoradiation may positively impact local control in N+ patients. These findings need to be validated in future clinical trials. Clinical trial information: NCT00789958.

Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma.

9501 Background: We assessed whether or not adjuvant pembrolizumab given over 1 year would improve OS and RFS in comparison to high dose ipilimumab (ipi10) or HDI - the two FDA-approved adjuvant treatments for high risk resected melanoma at the time of study design. Methods: Patients age 18 or greater with resected stages IIIA(N2), B, C and IV were eligible. Patients with CNS metastasis were excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel node positive disease. Prior therapy with PD-1 blockade, ipilimumab or interferon was not allowed. Two treatment arms were assigned based on stratification by stage, PD-L1 status (positive vs. negative vs. unknown), and intended control arm (HDI vs. Ipi10). Patients enrolled between 10/2015 and 8/2017 were randomized 1:1 to either the control arm [(1) interferon alfa-2b 20 MU/m2 IV days 1-5, weeks 1-4, followed by 10 MU/m2/d SC days 1, 3, and 5, weeks 5-52 (n=190), or (2) ipilimumab 10 mg/kg IV q3w for 4 doses, then q12w for up to 3 years (n=465)], or the experimental arm [pembrolizumab 200 mg IV q3w for 52 weeks (n=648)]. The study had three primary comparisons: 1) RFS among all patients, 2) OS among all patients, 3) OS among patients with PD-L1+ baseline biopsies. Results: 1,426 patients were screened and 1,345 patients were randomized with 11%, 49%, 34%, and 6% AJCC7 stage IIIA(N2), IIIB, IIIC and IV, respectively. This final analysis was performed per-protocol 3.5 years from the date the last patient was randomized, with 512 RFS and 199 OS events. The pembrolizumab group had a statistically significant improvement in RFS compared to the control group (pooled HDI and ipi10) with HR 0.740 (99.618% CI, 0.571 to 0.958). There was no statistically signifcant improvement in OS in the 1,303 eligible randomized overall patient population with HR 0.837 (96.3% CI, 0.622 to 1.297), or among the 1,070 (82%) patients with PD-L1 positive baseline biopsies with HR 0.883 (97.8% CI, 0.604 to 1.291). Gr 3/4/5 event rates were as follows: HDI 69/9/0%, ipi10 43/5/0.5% and pembrolizumab 17/2/0.3%. Conclusions: Pembrolizumab improves RFS but not OS compared to HDI or ipi10 in the adjuvant treatment of patients with high-risk resected melanoma. Pembrolizumab is a better tolerated adjuvant treatment regimen than HDI or Ipi10. Support: NIH/NCI NCTN grants CA180888, CA180819, CA180820, CA180863; and in part by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial Acknowledgement: With special thanks to Elad Sharon, MD, MPH, and Larissa Korde, MD, MPH. National Cancer Institute, Investigational Drug Branch, for their contributions to this trial, as well as Nageatte Ibrahim, MD, and Sama Ahsan, MD Merck. Clinical trial information: NCT02506153.

Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection.

High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown. This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay. A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P <0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P <0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P <0.001). Pain scores were comparable between groups. There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.

Management of The Posterior Cerebral Fossa Ependymomas

Background Posterior fossa brain ependymomas are one of the most devastating forms of human illnesses which are more common in children. Brainstem compression, herniation and death are the risks with tumours in this critical location. Patients and Methods: A retrospective study including 50 patients with posterior fossa ependymoma were performed at the Neurosurgery Department in Ait IDDIR University Hospital between the period of January 2005 and December 2015 . In each case, diagnosis was made clinically and confirmed radiologically and histo-pathologically.. All patients received the adjuvant treatment Results Out of 50 patients, 30 (60%) patients were males and 20 (40%) were females. The mean age was 24 years (ranged 5 months –47 years) ; we identified 29 (58%) children and 21 (42%) adults,. Ventriculo-peritoneal shunts were placed in all our patients, the total tumor excision was done to 35% and the partial tumor excision was done to 65% patients. The most common complications were as follows: Shunt malfunction : 4% , operative cavity hematoma 6%, CSF fistula 4%, deterioration of Cerebellar syndrome 6%, Cerebellar Mutism 2%, Mixed nerves palsy 4% and early post operative deaths 10%. Tumor architecture was classified as classic (Grade II) in 35 (70%) cases and anaplastic (Grade III) in 13(26%) cases. Adjuvant treatment regimens following resection included radiation therapy only (72%) for 36 patients including children above and adults and chemotherapy only (36%) for 9 children below 4 years and 9 recurrent tumors. During follow-up period, recurrence occurred in 27% 11patients out of 41patients .Five patients died (10%). Conclusion The surgical treatment of posterior fossa tumours still represents a challenge for neurosurgeons, Radical surgery with preservation of vital structures is the treatment of choice in patients with Posterior Cerebral Fossa ependymomas.. Our experience shows the accepted results, complications and surgical outcome in relation to previous clinical studies.

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer.

Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes. In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001. The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

Pertuzumab and trastuzumab as adjuvant treatment for HER2-positive early breast cancer: outcomes in Chinese patients in the APHINITY study.

The addition of pertuzumab to trastuzumab plus standard chemotherapy as adjuvant therapy following surgery significantly improved invasive disease-free survival (IDFS) in patients with HER2-positive early breast cancer in the multinational randomized APHINITY trial (NCT01358877, BIG 4-11/BO25126/TOC4939G). We analyzed clinical outcomes in the subgroup of patients recruited at Chinese sites. Patients were randomized to standard adjuvant chemotherapy plus 1year of trastuzumab with pertuzumab or placebo. Patients recruited in mainland China, Hong Kong and Taiwan are included in this descriptive analysis. Chinese patients had similar demographic characteristics to the global population, but a higher proportion had nodal involvement. Although this subgroup analysis was not powered to detect statistical significance, a numerical improvement in IDFS was observed with the addition of pertuzumab to trastuzumab in Chinese patients (hazard ratio, 0.69; 95% confidence interval: 0.39-1.19; 3-year IDFS event-free estimates 92.5% [pertuzumab] and 91.7% [placebo]), which was consistent with the primary analysis of the global population. Further subgroup analyses showed numerical improvements in the Chinese node-positive, hormone receptor-negative and -positive subgroups, although confidence intervals were wide due to the low number of events. The incidence of diarrhea was higher in the pertuzumab arm, and no primary cardiac events occurred in Chinese patients in either arm. Pertuzumab, used in combination with trastuzumab and chemotherapy in APHINITY, is effective as an adjuvant treatment regimen for Chinese patients with HER2-positive early breast cancer in a setting with curative intent. The safety profile in Chinese patients was consistent with that of the global population.

Adjuvant chemotherapy (AC) choices: An analysis of elderly Australian patients with stage III colorectal cancer (CRC).

16 Background: The optimal adjuvant treatment regimen for stage III CRC patients aged ≥70 years remains unclear. Subgroup analyses of randomised trials support the use of single agent fluoropyrimidines (FP) but no survival benefit has been observed for the addition of oxaliplatin. This study assessed rates of AC use in elderly patients with stage III CRC, analysed reasons why elderly patients did not receive AC and compared disease free survival (DFS) between those who did and did not receive AC. Methods: Data was analysed from the ACCORD-CRC registry, which prospectively collects treatment and outcome data from patients with CRC in Australia. All patients aged ≥70 years with resected stage III CRC from seven institutions between January 2005 and December 2018 were included. Where patients did not receive AC, reasons for this were documented prospectively. Using univariate analysis, baseline demographics and clinicopathological variables were compared between patients who were and were not offered AC. Differences were defined as statistically significant if a two-tailed p value was &lt; 0.05. DFS was defined as time from surgical resection to time of recurrence and cases of death without recurrence were censored at the time of death. Results: Data was obtained for 685 patients; median age was 78 years (range 70-97). AC was offered to 72% of patients; these patients were significantly more likely to be aged 70-74y (34% vs 12%, p &lt; 0.0001), have an ECOG score of 0-1 (88% vs 57%, p &lt; 0.0001), have proficient mismatch repair (pMMR) (87 vs 75%, p = 0.01) and T1-3 tumours (74% vs 65%, p = 0.02) compared to patients not offered AC. Nodal status and tumour differentiation did not differ significantly. 15% of patients offered AC declined systemic treatment. The most frequent documented reasons for not offering AC were age plus comorbidities, followed by comorbidities alone and age alone (42%, 29% and 23%, respectively). Of the patients who commenced AC, 27% received oxaliplatin-FP. These patients were significantly more likely to be aged 70-74y (71% vs 28%, p &lt; 0.0001), have an ECOG score of 0-1 (94% vs 87%, p = 0.04), have N2 disease (39% vs 26%, p = 0.02) and poorly differentiated tumours (42% vs 29%, p = 0.02) compared to those receiving FP alone. T-stage and MMR status did not differ significantly. After median follow up of 32 months, the 3-year DFS rate was higher for patients who received AC compared to those who did not (71% vs 64%; HR 0.72, p = 0.046) but no significant difference was observed for the addition of oxaliplatin (75% vs 69%; HR 0.76, p = 0.18) compared to FP alone. Conclusions: In this real world cohort, approximately 75% of elderly patients with stage III CRC were offered AC. Younger age, better performance status, pMMR and lower T stage were significantly associated with physicians offering elderly patients AC. Those who received AC had improved DFS compared to those who did not.

Ozone Therapy in Patients with the New Coronavirus Infection COVID-19

Aim. In our work we seek to develop new approaches for treating patients with COVID-19. The first reports about new coronavirus infection, COVID-19, came out in China in 2019. It was recognized by WHO as a pandemic crisis on March 11, 2020. Currently, there is no standard therapy protocol for COVID-19 and the drugs are used off label. Materials and methods. We have implemented ozone therapy into clinical practice as an adjuvant treatment regimen for patients with SARS-CoV-2 infection. In our study, 19 patients received ozone therapy and 18 patients were members of the control group. All patients had a positive PCR test for SARS-CoV-2 infection and were matched by the following features: sex, age, severity of symptoms, imaging data and clinical history. Patients in the study group received ozone therapy in the form of daily intravenous infusions of ozonized physiological solution (concentration: 2.2-2.4 mg/l). Conclusion. We observed a statistically significant improvement in laboratory, radiological and clinical tests of patients in the study group compared to the control group on the 14th day. Thus, we have demonstrated the benefits of using ozone therapy in patients with the new coronavirus infection COVID-19. Taking into consideration the physiological processes underlying such approach, ozone therapy should be justified for both phases: the beginning and at the peak of the disease.

Does Sequencing of Adjuvant Therapy Influence Outcome for Stage IIIC Endometrial Carcinoma? A Multi-institutional Analysis

In GOG-258, patients who received upfront chemoradiotherapy had more distant relapses compared to those treated with systemic chemotherapy alone, although vaginal and nodal recurrence rates were lower with the addition of adjuvant radiotherapy (RT). Given the importance of both systemic and local therapies, this study evaluates clinical outcomes by the sequence and type of adjuvant therapy for patients with stage IIIC endometrial cancer (EC). In a multi-institutional retrospective cohort study, clinical and treatment data from 12 academic centers were collected for patients with stage IIIC EC treated with curative intent. All patients had surgical staging and received chemotherapy and radiation. Adjuvant treatment (AT) regimens were classified as: adjuvant chemotherapy followed by sequential radiation (ACTRT), concurrent chemoradiation followed by chemotherapy (CCTRT), systemic chemotherapy before and after RT (Sandwich), adjuvant RT followed by chemotherapy (ARTCT) or chemotherapy concurrent with vaginal cuff brachytherapy alone (CCTBT). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by Kaplan-Meier method and covariates were compared by log-rank test. Chi-square tests were used to compare categorical variables. A total of 670 eligible patients were included (Table) with a median follow-up of 44.1 months. The estimated 5-year OS and RFS rates were 71.5% and 65.5%, respectively. On univariate analysis (UVA) for OS, older age, non-white race, non-endometrioid histology, grade 3 tumor, 2 or more positive nodes, adnexal involvement, cervical involvement, stage IIIC2 vs. IIIC1, and in-field recurrence were associated with worse OS (all p<0.02). On UVA for RFS, older age, non-endometrioid histology, grade 3 tumor, lymphovascular invasion, adnexal involvement, cervical involvement and stage IIIC2 were associated with recurrence. The sequence and type of adjuvant therapy was not correlated with OS or RFS (p = 0.08 and 0.8, respectively). The most common pattern of recurrence was distant metastasis only (66%). Site of first recurrence was significantly different by adjuvant treatment regimen (p = 0.02): ACTRT, CCTRT and Sandwich had a higher proportion of distant metastasis whereas ARTCT and CCTBT had more para-aortic nodal recurrences. Pelvic control was highest for ACTRT. The sequence and type of adjuvant therapy did not impact OS or RFS rates, which were comparable to those of the prospective GOG 258 and PORTEC-3 studies. Adjuvant radiotherapy resulted in excellent pelvic control. Most recurrences were distant despite upfront systemic chemotherapy given in most patients, highlighting the need for novel regimens.Abstract 102; TableFactornAge, Median62Race Caucasian African-American Other480 83 47Stage IIIC1 IIIC2430 240Histology Endometrioid Non-endometrioid441 229Grade 1-2 3320 346RT EBRT BT Both176 94 400Adjuvant therapy ACTRT CCTRT Sandwich ARTCT CCTBT290 112 165 26 77 Open table in a new tab

Adjuvant radiation followed by chemotherapy is associated with improved overall survival in endometrial cancer

ObjectiveAlthough multimodality therapy has been shown to improve outcomes for patients with high-risk endometrial carcinoma, optimal type and timing of adjuvant therapies is unknown. MethodsPatients with stage I-IVA endometrial carcinoma diagnosed from 2004 to 2015, and treated with surgery, chemotherapy, and radiation were identified in the National Cancer Database. Adjuvant treatment was categorized as sequential radiation followed by chemotherapy (RT-CT), concurrent chemoradiation (CCRT, RT and CT started within 7 days), or sequential chemotherapy followed by radiation (CT-RT). Analysis for propensity score matched (PSM) cohorts comparing RT-CT to CCRT and CT-RT groups was additionally performed. ResultsA total of 17,070 patients were identified, including 12,402 (72.7%) treated with RT-CT, 2,153 (12.6%) with CCRT, and 2,515 (14.7%) with CT-RT. Median follow-up was 44.3 months. Five-year overall-survival (OS) by adjuvant treatment regimen was 77.3% (95% CI 76.4%–78.2%), 74.3% (95% CI 72.0%–76.3%), and 74.4% (95% CI 72.5%–76.3%), respectively (p < .001). When unmatched cohorts were stratified by stage, adjuvant RT-CT was associated with improved OS in stage I and III patients. A similar survival advantage associated with RT-CT was observed in PSM cohorts comparing RT-CT group to CCRT/CT-RT group (5-year OS 77.4% vs 74.2%, p = .001). However, the difference in OS was significant only among stage III patients (RT-CT 73.9% compared to CCRT/CT-RT 69.7%, p =.002). ConclusionOur findings suggest survival benefit with adjuvant RT-CT compared to CT-RT or CCRT in patients undergoing trimodality therapy for endometrial cancer. This survival benefit may be limited to stage III patients.

Successful use of a therapeutic trial of graduated volume and dose escalation for postoperative head and neck radiotherapy in a Fanconi anemia patient

Patients with the heritable disease, Fanconi anemia (FA), have a 500-fold risk of developing head and neck squamous cell carcinomas (HNSCC). However, the use of conventional cytotoxic agents including radiation therapy and cisplatin-based chemotherapy is contraindicated in patients with FA due to underlying DNA repair defects. We present a young FA patient with recurrent HNSCC and high-risk pathologic features treated with a therapeutic trial of chemoradiation. This novel strategy employs a gentle radiation dose and volume escalation with concurrent pembrolizumab. The patient completed the entire course of therapy with no treatment delays or interruptions. The FA patient population has a clear need for adjuvant treatment regimens given their predilection for HNSCC. A therapeutic trial may allow FA and other radiosensitive patients to trial radiation with the option to terminate treatment before any severe side effects occur and for some to complete a full course of treatment.

Challenges in Preventing Bone Loss Induced by Aromatase Inhibitors.

Aromatase inhibitors have become a mainstay in the adjuvant treatment regimen in postmenopausal women with hormone receptor-positive breast cancer. While many of these patients have an excellent long-term prognosis, adverse effects on bone represent an emerging complication of aromatase inhibitor treatment, resulting in substantial bone loss and fragility fractures. Treatment approaches to prevent aromatase inhibitor-induced bone loss typically consist of an antiresorptive approach with bisphosphonates or the RANKL antibody denosumab. However, different guidelines vary with respect to treatment thresholds, duration, and dosing. The choice of antiresorptive regime is further complicated by comorbidities and potential disease-modifying effects of individual agents. This review summarizes the evidence of how aromatase inhibitors affect bone health and provides an update of clinical approaches to preserve bone strength in affected women. (J Clin Endocrinol Metab XX: 0-0, 2020).

Recurrence of appendix tumor: case report and literature update

Herein, we report a case of appendix adenocarcinoma who presented with a recurrence 8 years after the initial diagnosis. A 54-year-old male underwent appendectomy in 2009. The pathology revealed a 1.7 cm diameter low grade mucinous carcinoid tumor. Any additional treatment was not recommended for patient other than appendectomy. The patient was admitted with the symptoms of ileus at 8 years after surgery and then underwent to right hemicolectomy in 2017. On histopathological examination of the specimen revealed a Goblet cell adenocarcinoid tumor, arising from iliocecal valv with pericolorectal tissue invasion of 5 cm in diameter. Lymph-node metastases were found in 16 dissected lymph nodes. The patient was initiated to treat with combined capecitabine and oxaliplatin chemotherapy. There is no clear evidence to support the superiority of any particular chemotherapy regimen for adjuvant treatment of appendix tumors. In this regard more studies are needed to use combined regimens.

The Multi-Disciplinary Management of Gastric Adenocarcinoma: The Retrospective Analysis of Outcomes of Patients Treated at Vajira Hospital

Background: Gastric adenocarcinoma is an uncommon gastrointestinal cancer in Thailand. The pathological features, pattern of relapses, treatments, and outcomes have not been explored systemically. Objective: The primary outcome was to determine overall survival (OS) of patients. The secondary outcomes were to explore pathological features, pattern of relapses, outcomes of adjuvant and palliative treatments, and prognostic factors of survival. Materials and Methods: The investigators conducted a retrospective analysis of patients with gastric cancer diagnosed between January 1, 2010 and December 31, 2015 and received medical attention at Vajira Hospital. Demographic data including gender, age, health schemes, histologic types, staging, surgical methods, paradigms of adjuvant treatment, metastatic sites, and chemotherapy regimens. Results: There were 90 gastric cancer patients with adequate clinical data. The median age was 60 years (IQR 50 to 69). Most of them had infiltrative (poorly differentiated or signet-ring cell) histology (67, 74.4%) and presented with metastatic disease (42, 46.7%). The median OS of patients with stage 1/2, 3, and 4 were 85 months (IQR 19 to NR), 25 months (IQR 13 to 43), and 5 months (IQR 2 to 15), respectively. The investigators did not find the OS difference between patients receiving adjuvant chemoradiation compared to adjuvant chemotherapy. Among patients with non-metastatic diseases, patients who underwent total gastrectomy and patients with T3 to T4 were the independent factors of poor disease-free survival. Peritoneal carcinomatosis was the most common site of metastasis. Conclusion: The outcomes of patients with gastric cancer in Thailand was poor due to the advanced stage at presentation. Compared to other parts of the world, gastric cancer in Thailand has many different features. Keywords: Gastric cancer, Survival, Multi-disciplinary treatment, Thailand

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluatetheprognostic factors associated with clinical outcomes. Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. A total of 108 patients were identified with a median follow-up of 31.7months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.

Long-term (up to 16\xa0months) health-related quality of life after adjuvant tailored dose-dense chemotherapy vs. standard three-weekly chemotherapy in women with high-risk early breast cancer

PurposeTo prospectively compare HRQoL effects of two modern adjuvant chemotherapy breast cancer treatment regimens at six time-points up to 16 months after random assignment.MethodsThe open-label, randomized, Phase 3 “Panther trial” was conducted between February 2007 and September 2011. 760 women, aged 65 years and younger, after surgery for non-metastatic node-positive or high-risk node-negative breast cancer were randomized 1:1 to the experimental group (four cycles of tailored and dose-dense adjuvant epirubicin and cyclophosphamide/2 weeks followed by four cycles of tailored dose-dense docetaxel/2 weeks) or standard group (three cycles of fluorouracil and epirubicin-cyclophosphamide/3 weeks followed by three cycles of docetaxel/3 weeks). HRQoL was assessed at all Swedish centres using EORTC QLQ-C30 and EORTC QLQ-BR23 at six points during 16 months before randomization.ResultsResponse rates to questionnaires were highest at baseline 728/780 (93%) and lowest 16 months after randomization, 557/750 (74%). HRQoL declined during treatment in both groups. At the end of treatment, the experimental group reported statistically significantly lower HRQoL (P < 0.001) than the standard group on global health status, physical functioning, role functioning, social functioning, fatigue, sexual functioning, and systemic therapy effects. No differences were found for emotional functioning, body image, and arm and breast symptoms. There were no statistically significant differences between the groups at the first follow-up and at subsequent assessments. HRQoL levels at the 16-month follow-up were similar to baseline values.ConclusionsNegative HRQoL impact of the dose-dense and tailored strategy appears to be prominent during treatment, but HRQoL recover once treatment ends.Trial Registration clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier:ISRCTN39017665.

Primary malignant melanoma of the female urethra: Twenty years of surgical and medical management at a tertiary referral center.

430 Background: Malignant melanoma of the female urethra accounts for less than 1% of all melanoma and less than 4% of urethral cancer. Due to limited data regarding management and outcomes of this condition, we evaluated the management and outcomes of urethral melanoma in females over the last 20 years at our institution. Methods: Patients were identified via retrospective review of the medical record. Those with metastatic disease at initial diagnosis were excluded. We evaluated primary and adjuvant treatments, disease recurrence and overall survival. Results: Fifteen women (median age 71, range 55, 82) were identified. Majority of masses involved the distal urethra (86.6%). All patients underwent primary surgical resection (60.0% partial urethrectomy, 40.0% radical urethrectomy). Disease recurrence and metastatic spread occurred in 73.3% (median 7 months, IQR 4, 12) and 60% (median 6 months, IQR 3, 9) of patients, respectively. 90.9% of patients with recurrence received adjuvant therapy: 5 chemotherapy and radiation, 4 chemotherapy only, 1 anterior exenteration. Of the 9 patients undergoing chemotherapy, treatment regimens were varied and included checkpoint inhibitors (2/9), platinum-based chemotherapy (3/9), tyrosine kinase inhibitors (2/9), taxels (2/9), and alkylating agents (1/9). Median overall survival was 27 months (IQR 7.5, 57.5). Conclusions: Malignant melanoma of the urethra is locally aggressive with a high likelihood of recurrence and metastases resulting in poor long-term survival. Despite high recurrence rates, our data highlight the lack of consensus adjuvant treatment regimens. Future research is required to identify neoadjuvant, combination, and adjuvant treatment approaches to improve disease outcomes.

Changes in bone mineral density during 5years of adjuvant treatment in premenopausal breast cancer patients.

Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer. Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T). After 5years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5years of treatment (all p < 0.005). Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

Abstract GS1-08: Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial

Abstract Background: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) comprises a taxane and an anthracycline. Concomitant capecitabine may add efficacy benefits, but robust data are lacking. The efficacy and safety of capecitabine integration into the TNBC adjuvant treatment regimen was evaluated. Methods: This was a randomised, open-label, phase 3 trial conducted in China (ClinicalTrials.gov identification NCT01642771). Post-resection, eligible female patients with early TNBC were randomly assigned (1:1) to either capecitabine treatment (3 cycles of capecitabine and docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine [TX-XEC]), or control treatment (3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil [T-FEC]). Randomisation was centralised without stratification. The primary endpoint was 5-year disease-free survival (DFS). Findings: Between June 2012 and November 2013, 585 patients were randomized to treatment (capecitabine, n=297; control, n=288), of whom 561 were treated per protocol (n=288 and n=273, respectively). Median follow-up was 67 months. The 5-year DFS rate was longer with capecitabine than with control treatment (86·26% vs. 80·23%, hazard ratio 0·66, 95% confidence intervals 0·44-0·98; p=0·038). The 5-year overall survival rates were similar (93·27% vs. 90·55%, respectively). Overall, 38·89% patients had capecitabine dose reductions and 8·42% reported grade 3/4 hand-foot syndrome. The most common grade 3/4 hematologic toxicities were neutropenia (capecitabine 136 [45·79%] patients vs. control 119 [41·32%] patients) and febrile neutropenia (49 [16·5%] vs. 46 [15·97%] patients). Safety data were in line with the known capecitabine safety profile and generally comparable between arms. Interpretation: Capecitabine, when administered concomitantly with standard adjuvant taxane/anthracycline chemotherapy, significantly improved DFS rates in TNBC, with no new safety concerns. Table 1: Baseline patient demographics and clinical characteristics (PPS population; n=561)T-FEC (n=273)TX-XEC (n=288)pAge (years), mean ± SD48.30 ± 8.7649.07 ± 10.440·3501BSA (m2), mean ± SD1.60 ± 0.111.60 ± 0.110·4209Menstruation0·2946Premenopausal61·5757·09Postmenopausal38·4342·91Family History26·3726·830·9029Operation TypeBreast conserving21·8525·090·3683Mastectomy78·1574·91SLNB28·5226·130·5275Axillary dissection71·4873·87Node Stage0·5967N065·0665·97N123·7925·35N26·323·82N34·834·86T Stage0·2938T1a,b4·172·33T1c42·5041·25T250·4255·25T32·921·17Histology0·7190IDC89·6390·24ILC0·741·39Other9·638·36Grade0·2322I3·832·94II47·6640·76III48·5156·30Ki67 ≥30%+87·2185·770·6245LVI +14·8110·100·1363Surgery-to-chemo time (days), mean ± SD16·94 ± 7·7717·99 ± 9·240·1581Data are % except where specified.BSA=body surface area; IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma; LVI=lymphovascular invasion; PPS=per protocol set; SD=standard deviation;Table 2: Number of events (PPS population; n=561)T-FECTX-XEC(n=273)(n=288)Any event57 (20·88)41 (14·24)Second primary4 (1·47)5 (1·74)Contralateral breast5 (1·83)6 (2·08)Local recurrence18 (6·59)7 (2·43)Ipsilateral breast/Chest135Regional lymph nodes83Distant recurrence37 (13·55)29 (10·07)Liver37Lung1714Bone67Other2714Death26 (9·52)19 (6·60) Citation Format: Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Sheng, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Zhimin Shao, Chinese Breast Cancer Study Group (CBCSG) 010. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS1-08.