Selection Of Patients For Chemotherapy Research Articles

Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer.

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.

Disparity of treatment-related adverse events and outcome in patients with early-onset metastatic colorectal cancer (mCRC).

6560 Background: While the incidence of newly diagnosed early-onset mCRC has been increasing, disparity of treatment-related adverse events (AE) and outcomes of this patient population has been inadequately studied with inconclusive findings. We aimed to evaluate such age-related disparity and explore potential underlying causes. Methods: We used individual patient data from 3 clinical trials in Project Data Sphere where 756 and 467 patients with mCRC received first-line FOLFOX in study 1 (NCT 00305188, NCT00272051) and study 2 (NCT00364013), respectively. Clinical NGS data of 763 patients with mCRC from prospectively maintained Moffitt Clinical Genomics Database were used to assess genomic alterations. Patients were categorized into 3 age groups: <50, 50-65, and >65 years. Continuous and categorical variables were compared with t test and χ2 test, respectively. Kaplan-Meier method and log-rank test were used for survival analysis. Benjamini-Hochberg procedure was used to adjust for multiple comparisons. Results: Among 1986 patients included, 341 (17.2%) in the <50 group, 912 (45.9%) in the 50-65 group, 733 (36.9%) in the >65 group had similar baseline characteristics. Outcomes: Patients in the <50 group had shorter median OS compared to the 50-65 (15.5 vs 20.5 month, p=0.003) and >65 groups (15.5 vs 20.8 months, p=0.004) and shorter median PFS compared to the 50-65 (8.1 vs 9.4 month, p=0.039) and >65 groups (8.1 vs 8.6 months, p=0.07) in study 1. Findings were confirmed in study 2. Toxicity: Compared to other age groups, the <50 group had a higher incidence of severe (grade≥3) abdominal pain (8.4% vs 3.4%, p=0.01), severe anemia (6.1% vs 1.2%, p=0.001), nausea/vomiting (69.3% vs 58.8%, p=0.02), but lower incidence of severe diarrhea (6.1% vs 10.8%, p=0.02), severe neutropenia (25.7% vs 44.2%, p<0.001), and severe fatigue (4.5% vs 7.3%, p=0.02). The <50 group had earlier onset of nausea/vomiting (1.0 vs 2.3 weeks, p=0.01), mucositis (3.6 vs 5.4 weeks, p=0.05), and neutropenia (8.0 vs 9.0 weeks, p=0.04), and shorter duration of mucositis (0.6 vs 0.9 weeks, p=0.006). Outcomes + toxicity: In the <50 group, abdominal pain was associated with worse OS (HR 1.6, p=0.01). In contrast, fatigue (HR 0.66, p=0.03) and mucositis (HR 0.67, p=0.046) were associated with better OS. Neuropathy was associated with better PFS (HR 0.61, p=0.009). Genomics: Our NGS data showed that the <50 group had more ERBB2 amplification (10.5% vs 4.0%, p=0.04) and a trend of more TP53 mutations (80.2% vs 72.0%, p=0.07). These findings were confirmed in an independent mCRC cohort (n=471, MSK, Gastroenterology 2020). Conclusions: Patients with early-onset mCRC had worse outcome and unique treatment-related AE patterns. Distinct genomic profiles could explain some of the disparities. Our findings might improve a personalized management approach in patient selection for chemotherapy, counseling and AE monitoring.

Postoperative and Survival Outcomes After Cytoreductive Surgery in the Treatment of Metastatic Upper Tract Urothelial Carcinoma

To analyze utilization and outcomes of cytoreductive surgery (CRS) after systemic chemotherapy in select patients with metastatic upper tract urothelial carcinoma (UTUC). We identified 1,73 patients with cM1 UTUC from the National Cancer Database who were treated with first-line multiagent chemotherapy from 2004 to 2015. Patients considered surgical candidates based on Charlon-Deyo performance score were stratified into nonsurgical versus surgical arms based on receipt of CRS after systemic therapy. Those receiving radiation, immunotherapy, or other types of treatment were excluded. Cox proportional hazard models were used to analyze prognostic factors for overall survival (OS). Propensity-score matching and inverse probability of treatment weighting-adjusted regression models were used to compare OS. A total of 1182 patients were included of which 349 (29.5%) were treated with definitive surgery. Median follow-up was 64 months (95% confidence interval:49.8-79.4) for chemotherapy+surgery versus 61.2 (52.2-78.7) for the chemotherapy-alone arms (P=.09). Patients treated with surgery were younger and more commonly treated at academic facilities. Patients who received CRS had improved median-OS versus those treated with chemotherapy alone (13.7 vs 10.8 months, log-rank P-value <.001). Predictors of OS were performance score, treatment at academic facility, and performance of CRS. Furthermore, in propensity-score and inverse probability of treatment weighting-adjusted Cox regression analyses, CRS was associated with significant OS benefit (hazard ratios=0.61, 95% confidence interval:0.49-0.77, and 0.63;0.55-0.72; respectively). We provide a contemporary report on the survival benefit of CRS after treatment with systemic therapy for M1 UTUC patients. Longitudinal studies are needed to evaluate the role of surgery, when feasible, within multidisciplinary approaches for this relatively, rare disease.

The role of local radiotherapy following rituximab-containing chemotherapy in patients with transformed indolent B-cell lymphoma.

ObjectivesThis study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab‐containing chemotherapy.MethodsWe retrospectively analysed 92 patients with biopsy‐confirmed HT undergoing rituximab‐containing chemotherapy at our institution between 2003 and 2015.ResultsOf the 36 patients with limited‐stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5‐year progression‐free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28‐108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow‐up period. One patient developed hypothyroidism due to LRT; the others had no acute or late‐onset complications of LRT.ConclusionsOur data support the recommendation of LRT for HT lesion treatment following rituximab‐containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity.

English

BACKGROUND As most cases of head and neck cancer are locally advanced, i.e., stage III and IV, it may be useful to compare induction chemotherapy policies accompanied by simultaneous chemoradiation with concomitant chemoradiation alone, in terms of tumour response and toxicity profile in these cases. That's why this study was undertaken. We wanted to evaluate induction chemotherapy accompanied by chemoradiation in terms of local regulation as opposed to chemoradiation alone in locally advanced Head and Neck Cancers. METHODS This is a prospective comparative study. Study was done between July 2017 and July 2019, with Arm A (Test Group) &amp; Arm B (Control group). Forty patients of locally advanced Head and Neck cancer from the outpatient department, selected for treatment, were included in the study, with 20 in each arm. RESULTS Reduction in tumour size after treatment was compared in both the groups with RECIST (Response Evaluation Criteria in Solid Tumours) 1.1. Induction chemotherapy caused significant reduction in tumour size but had more toxicities which were manageable. When compared to conventional chemoradiation, the induction chemo group did not show statistically significant benefit. Response was better in patients with high nodal volume as some of the cases showed good response in the nodal volume irrespective of response of the primary. CONCLUSIONS This study emphasizes the role of induction chemotherapy in select patients with advanced disease, especially in high volume, where majority of cases (more than 80 %) are stage III or IV and above. Hence, patient selection is the key to outweigh the risk involved. KEYWORDS Cancer Undergoing Radiation Therapy

Chemotherapy, not androgen receptor-targeted therapy should be used upfront for metastatic hormone-sensitive prostate cancer. PRO: docetaxel chemotherapy should be the default consideration in metastatic hormone-sensitive prostate cancer.

Chemotherapy, not androgen receptor-targeted therapy should be used upfront for metastatic hormone-sensitive prostate cancer. PRO: docetaxel chemotherapy should be the default consideration in metastatic hormone-sensitive prostate cancer.

Management of colon cancer patients: A comprehensive analysis of the absence of multidisciplinary team meetings in two French departments

The care management of colorectal cancers has evolved, particularly since the implementation of multidisciplinary team meetings (MDTm). The aim of this study was to identify factors associated with the non-presentation of colon cancer patients in MDTm (no-MDTm) and to assess the association between no-MDTm and the diagnostic and therapeutic care management, in two areas in France, in 2010. Patients over 18 years diagnosed for invasive colon cancer in Gironde and Tarn during 2010 were included from the cancer registries of these two departments. We used five indicators to evaluate the care management of colon cancer patients (about diagnosis, treatment and selection of patients for chemotherapy). No-MDTm patients were more likely to die early after diagnosis (OR=2.94, 95% CI=[1.52-5.66]). Elderly patients and those living in more disadvantaged areas were less often presented in MDTm (OR≥85years=2.10, 95% CI=[1.06-4.18]; OREDIQ4-Q5=1.96, 95% CI=[1.23-3.14]). After adjusting for patient-related variables (age, comorbidities, deprivation) and tumor (stage at diagnosis), we found that thoracic CT scan was less often performed among no-MDTm patients (OR=0.40, 95% CI=[0.24-0.65]). There was no association between the absence of MDTm and the therapeutic care management indicators. In conclusion, therapeutic care management was not associated with the absence of MDTm but with patient and tumor characteristics, including age, comorbidities and level of deprivation, that influence the non-presentation in MDTm.

Outpatient intensive induction chemotherapy for acute myeloid leukemia and high-risk myelodysplastic syndrome

AbstractTo improve patient quality of life and reduce health care costs, many conditions formerly thought to require inpatient care are now treated in the outpatient setting. Outpatient induction chemotherapy for acute myeloid leukemia (AML) may confer similar benefits. This possibility prompted a pilot study to explore the safety and feasibility of intensive outpatient initial or salvage induction chemotherapy administration for adults with AML and high-risk myelodysplastic syndrome (MDS). Patients with no significant organ dysfunction and a treatment-related mortality (TRM) score corresponding to a day 28 mortality rate of <5% to 10% were eligible for study. Patients were treated as outpatients with daily evaluation by providers and only admitted to the hospital if mandated by complications. Twenty patients were consented, and 17 were treated. Eight patients received initial induction chemotherapy and 9 received salvage induction chemotherapy. Fourteen patients completed induction chemotherapy administration in the outpatient setting (82.4%; exact 95% confidence interval [CI], 55.8-95.3). Three patients were admitted during the course of chemotherapy administration, 2 for neutropenic fever and 1 for grade 3 mucositis. No patients died within 14 days of the initiation of induction chemotherapy (exact 95% CI, 0-22.9). Results of this pilot study suggest it is feasible to complete outpatient induction chemotherapy in select patients with AML and high-risk MDS. A team including nurses, social workers, medical providers, and pharmacists was key to the successful implementation of outpatient induction.

SARCOMA METASTASIS CAUSING ATRIAL FIBRILLATION AND REFRACTORY PLEURAL EFFUSION

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Lungs are a primary site for metastasis of sarcomas, however malignant pleural effusion, which indicates a more widespread disease, are much rarer representing only 1-6% of all malignant effusions. We describe a case of a young man with a low-grade pelvic sarcoma that had progressive metastatic lung disease who went on to develop a refractory pleural effusion and new-onset atrial fibrillation CASE PRESENTATION: A 43-year-old male diagnosed with low-grade sarcoma in the pelvis had undergone a left hemipelvectomy. Nine months later he developed metastatic disease and underwent radiation/chemotherapy and eventually Nivolumab trial with no improvement of the disease. The patient then presented three months later with respiratory distress and atrial fibrillation (Afib). A Computed Tomography Scan(CT) of the chest showed increased muscular, bone, lung, and now pleural/ possible pericardial metastases. The CT also showed a large right-sided pleural effusion. The patient underwent thoracentesis with pleural fluid analysis demonstrating an exudative effusion, with cytology showing rare atypical large cells with high nuclear/cytoplasmic ratio consistent with malignant pleural effusion. Echocardiogram showed a new pericardial space mass likely a metastatic deposit. It was felt that mass contributes to persistent Afib. Due to recurrent pleural effusions, the patient received a PleurX catheter. This PleurX catheter initially drained well but later failed to continue to drain fluid and was removed. He later required admission to ICU due to acute hypoxic and hypercapnic respiratory failure. The patient failed to improve with non-invasive ventilation. The family declined intubation and the patient passed away on comfort measures. DISCUSSION: Metastatic pulmonary metastases arise most commonly in patients with malignant fibrous histiocytoma, synovial sarcoma, liposarcoma, & leiomyosarcoma, especially if histology is high grade. Lower grade sarcomas are considered more indolent and lung metastatic rate is lower. In our case, the patient had low-grade sarcoma which makes it more unusual. Complete resection of metastasis, when feasible, is the most important factor in determining post-metastasis survival, with the median survival of 33 months vs median survival of 11 months if resection is not done. This was not able to be done in our patient. When metastasis to the pericardium occurs it is common to see arrhythmias on ECG; the most common being PAC’s, PVC’s, and SVT's such as Afib as in our patient CONCLUSIONS: Metastatic progression of sarcoma to the lung can be managed surgically and with chemotherapy in select patients but prognosis remains poor. Pleural involvement, especially with malignant effusion, portends a very poor prognosis Reference #1: Cates CU, Virmani R, Vaughn WK, et al. Electrocardiographic markers of cardiac metastasis. Am Heart J 1986;112:1297–303. Reference #2: Marulli G, Mammana M, Comacchio G, Rea F. Survival and prognostic factors following pulmonary metastasectomy for sarcoma. J Thorac Dis. 2017;9(Suppl 12):S1305-S1315. Reference #3: Yildirim H1, Metintaş M, Ak G, Dündar E, Erginel S. Soft tissue sarcoma metastatic to pleura. Tuberk Toraks. 2008;56(2):197-200 DISCLOSURES: No relevant relationships by Edward Conuel, source=Web Response No relevant relationships by Lezah McCarthy, source=Web Response No relevant relationships by Kristoffer Neu, source=Web Response No relevant relationships by Raina Patel, source=Web Response No relevant relationships by Muhammad Salick, source=Web Response No relevant relationships by Ali Wazir, source=Web Response No relevant relationships by Robert Wilcott, source=Web Response

Prognostic immunohistochemical biomarkers of chemotherapy efficacy in biliary tract cancer: A systematic review and meta-analysis.

Chemotherapy is the mainstay of systemic treatment of biliary tract cancer (BTC). However, the treatment response to chemotherapy varies between patients. Currently, no prognostic biomarkers for chemotherapy efficacy have been considered for use in clinical practice. A systematic review was conducted to evaluate the prognostic value of immunohistochemical biomarkers for chemotherapy in patients with resected as well as with advanced BTC. Medline and EMBASE databases were searched up to March 2017 for studies that evaluated biomarker expression by immunohistochemistry in resected or advanced BTC patients treated with chemotherapy. The primary endpoints were overall survival (OS) and disease or progression free survival (DFS or PFS). Twenty-six studies, including a total of 1348 patients and 26 different biomarkers, met the inclusion criteria and were included in this review. The most frequently studied prognostic biomarkers in BTC were the human Equilibrative Nucleoside Transporter 1 (hENT1), Ribonucleotide Reductase M1 (RRM1), and excision repair cross-complementation 1 (ERCC1). In the meta-analysis of patients treated with gemcitabine-based chemotherapy, high hENT1 expression was associated with longer OS (HR 0.43, 95% CI: 0.28 to 0.64) and DFS/PFS (HR 0.45, 95% CI: 0.33 to 0.61). hENT1 is a promising prognostic biomarker for gemcitabine-based chemotherapy in resected as well as in advanced BTC and should be further validated for the selection of patients for chemotherapy.

A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer

BackgroundThe response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in 3 decades. ObjectiveTo identify genes that influence cisplatin resistance in bladder cancer. Design, setting, and participantsWe performed a whole-genome CRISPR screen in a bladder cancer cell line to identify genes that mediate resistance to cisplatin. Outcome measurements and statistical analysisTargeted validation was performed in two bladder cancer cell lines. The top gene candidate was validated in a publicly available bladder cancer dataset. Results and limitationsFrom the CRISPR screen, we identified MSH2 as the most significantly enriched gene and mismatch repair as the most significantly enriched pathway that promoted resistance to cisplatin. Bladder cancer cells with knockdown of MSH2 showed a reduction in cisplatin-mediated apoptosis. MSH2 loss did not impact the sensitivity to other chemotherapies, including the cisplatin analog oxaliplatin. Bladder tumors with low MSH2 protein levels, quantified using reverse-phase protein array, showed poorer survival when treated with cisplatin- or carboplatin-based therapy; these results require future validation using immunohistochemistry. Additionally, results are retrospective from patients with primarily high-grade tumors; thus, validation in a controlled clinical trial is needed. ConclusionsWe generated in vitro evidence that bladder cancer cell lines depleted of MSH2 are more resistant to cisplatin. We additionally found an association between low MSH2 in bladder tumors and poorer patient survival when treated with platinum-based chemotherapy. If successfully validated prospectively, MSH2 protein level could assist in the selection of patients for chemotherapy. Patient summaryWe report the first evidence that MSH2 protein level may contribute to chemotherapy resistance observed in muscle-invasive bladder cancer. MSH2 has potential as a biomarker predictive of response to platinum-based therapy.

Combination of primary tumor location and mismatch repair status guides adjuvant chemotherapy in stage II colon cancer.

BackgroundCurrent opinions on the benefits of adjuvant chemotherapy for stage II colon cancer are divided and reformative election of these patients is required. We examined whether the primary tumor location based on mismatch repair status and other risk factors could better inform the current guideline.Materials and MethodsA total of 673 consecutive patients with stage II colon cancer were included in the analysis. Differences in the common clinicopathological factors between left-sided colon cancer and right-sided colon cancer were analyzed using Fisher's exact analysis. Kaplan–Meier analysis was used to distinguish the survival difference by primary tumor location and/or MMR status.ResultsRCC had a shorter overall survival (P = 0.001) and Disease-free survival (P = 0.050) than LCC but was associated with survival benefit from adjuvant chemotherapy (P = 0.001 and P = 0.011 for OS and DFS, respectively). Mismatch repair-proficient had a shorter OS (P = 0.036) and disease free survival (P = 0.034) than mismatch-repair deficient but chemotherapy improved the OS (P = 0.007). When the primary tumor location and MMR status were combined, the PMMR/RCC was the only subgroup that could benefit from adjuvant chemotherapy (P < 0.001 and P = 0.002 for OS and DFS, respectively). Other tumors such as DMMR/RCC, DMMR/LCC, and PMMR/LCC did not benefit.ConclusionsThe observed survival benefits in PMMR/RCC patients treated with adjuvant chemotherapy will allow better selection of patients for chemotherapy who are in stage II.

Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer

The Notch signaling pathway mediates cell fate decisions1,2 and is tumor suppressive or oncogenic depending on the context2,3. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine (NE) fate4–6. In small cell lung cancer (SCLC), an aggressive NE lung cancer7, loss-of-function NOTCH mutations and the inhibitory effects of ectopic Notch activation indicate that Notch signaling is tumor suppressive8,9. Here, we show that Notch signaling can be both tumor suppressive and pro-tumorigenic in SCLC. Endogenous activation of the Notch pathway results in a NE to non-NE fate switch in 10-50% of tumor cells in a mouse model of SCLC and in human tumors. This switch is mediated in part by Rest/Nrsf, a transcriptional repressor that inhibits NE gene expression. Non-NE Notch-active SCLC cells are slow growing, consistent with a tumor suppressive role for Notch, but these cells are also relatively chemoresistant and provide trophic support to NE tumor cells, consistent with a pro-tumorigenic role. Importantly, Notch blockade in combination with chemotherapy suppresses tumor growth and delays relapse. Thus, SCLC tumors generate their own microenvironment via activation of Notch signaling in a subset of tumor cells, and the presence of these cells may serve as a biomarker for the use of Notch pathway inhibitors in combination with chemotherapy in select SCLC patients.

Abstract B14: Neoantigen burden associates with chemoresponse in muscle-invasive bladder cancer patients receiving neoadjuvant chemotherapy

Abstract Background: The basis of response to chemotherapy is incompletely characterized. The immune system is increasingly recognized as both a key player in cancer control and as druggable target. We hypothesized that the immune system impacts pathologic response in patients undergoing cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive (≥pT2) bladder cancer though neoantigens present in tumors. Methods: Whole exome sequencing (WES) was performed on tumor DNA from patients in two independent cohorts who underwent cisplatin-based NAC. Pathologic response was defined in the cystectomy specimen. The Memorial Sloan Kettering/Dana Farber Cancer institute (MSKCC/DFCI) cohort (n=50; 25 ≤ pTis responders) and Philadelphia cohorts (n=48; 20 ≤ pTis responders) were treated with gemcitabine/ cisplatin or methotrexate/ vinblastine/ doxorubicin/ cisplatin. Mutation analysis was performed using standard analytical pipelines. Macrohistocompatibility complex (MHC)-restricted neoantigens were identified with netMHCpan and PolySolver. Wilcoxon rank sum test was used to test for significance and all tests were two-sided. Results: In both cohorts, mutation rate associated with pathologic response (p&amp;lt;0.01 and p&amp;lt;0.001 in Philadelphia and MSKCC/DFCI cohorts, respectively). In the MSKCC/DFCI cohort, the median predicted high affinity (Kd&amp;lt;500 nM) neoantigen count was 311 versus 154 for responding and nonresponding tumors, respectively (p=0.002). For the Philadelphia cohort, the median neoantigen count was 439 versus 218 for responding and nonresponding tumors, respectively (p=8.2 x 10-7). The relationship between neoantigen density and response maintained significance independent of the definition of response (pT0, ≤ pTis, ≤ pT1) and independent of the neoantigen Kd (500 nM, 100 nM, 50 nM) in both cohorts and when cohorts were combined. Conclusions: Mutational load and neoantigen burden correlate strongly with pathologic response to NAC. Chemotherapy may therefore exert tumor cell autonomous effects through apoptotic mechanisms and a tumor cell extrinsic effect by alerting the immune system via neoantigen presentation on dying cells. Mutation rate is likely directly correlated to neoantigen burden and both may impact patient selection for chemotherapy alone or in combination with immunotherapy agents, and development of antitumor vaccines. Experiments are underway to more directly characterize the impact of the immune system in the response to chemotherapy. Citation Format: Philip H. Abbosh, David Liu, Michael H. Johnson, Wafik S. El-Deiry, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen. Neoantigen burden associates with chemoresponse in muscle-invasive bladder cancer patients receiving neoadjuvant chemotherapy. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B14.

Cytotoxic chemotherapy in the contemporary management of metastatic castration-resistant prostate cancer (mCRPC).

For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long-term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration-sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies.

Efficient design of a phase III trial of competing tests for personalised cancer treatment in the absence of gold standard outcome data: challenges and potential solutions

The OPTIMAprelim pilot trial in early breast cancer aims to select multi-parameter tests for inclusion in a phase III trial evaluating their use for patient selection for chemotherapy. Patients are randomised between universal chemotherapy or test-directed chemotherapy. A key criterion for inclusion of a test as a comparator will be the expected value of further research into its clinical and cost-effectiveness.

Fractionated Stereotactic Radiosurgery for Reirradiation of Head-and-Neck Cancer

Stereotactic radiosurgery (SRS) is an appealing treatment option after previous radiotherapy because of its precision, conformality, and reduced treatment duration. We report our experience with reirradiation using fractionated SRS for head-and-neck cancer. From 2002 to 2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8), nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n = 23). Thirty-eight patients were treated definitively and 27 patients with metastatic disease and/or untreated local disease were treated palliatively. Nine patients underwent complete macroscopic resection before SRS. Thirty-three patients received concurrent chemoradiation. The median initial radiation dose was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5 fractions. Median follow-up for surviving patients was 16 months. Fifty-six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had partial, and 11 (20%) had no response. Median overall survival (OS) for all patients was 12 months. For definitively treated patients, the 2-year OS and locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate analysis demonstrated that higher total dose, surgical resection, and nasopharynx site were significantly associated with improved LRC; surgical resection and nonsquamous histology were associated with improved OS. Seven patients (11%) experienced severe reirradiation-related toxicity, including one treatment-attributed death. SRS reirradiation for head-and-neck cancer is feasible. This study demonstrates encouraging response rates with acceptable toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select patients warrants further study.

A prospective study of FOLFOX7 scheme as neoadjuvant chemotherapy for stage III gastric adenocarcinoma

To evaluate the efficacy and safety of FOLFOX7 scheme as neoadjuvant chemotherapy in patients with stage III gastric adenocarcinoma. From May 2005 to May 2007, 27 patients with stage III gastric adenocarcinoma were given neoadjuvant chemotherapy with FOLFOX7 scheme. Gastroscopy, endoscopic ultrasonography, abdominal B ultrasonography and abdominal CT was taken before chemotherapy and after 2 - 4 cycles of neoadjuvant chemotherapy to evaluate the objective response rate of the tumor. Then operations were carried out and the pathological responses was evaluated in those cases. The safety, objective response rate and pathological rate of neoadjuvant chemotherapy was assessed according to NCI-CTC v3.0, RECIST 2000, and the criteria established by Japanese Research Society for Gastric Cancer, respectively. R0 resection rate and surgery-related complications was also assessed in this group. The treatment was well tolerated, no grade 3 - 5 toxicity was observed. Complete response was obtained in 1 case, and partial response in 18 patients, overall response rate was 70.4% (19/27). Twenty-six patients received operation and R0 resection rate was 88.4% (23/26); no patient died in the perioperative period. The pathological response rate of patients had R0 excision was 60.9% (14/23). FOLFOX7 scheme as neoadjuvant chemotherapy for selected patients with stage III gastric adenocarcinoma can be well tolerated, it could induce tumor down-staging and improve R0 resection rate, although the long term efficacy remains to be evaluated.

Targeted lymph node evaluation in colorectal cancer: A decade of progress!

Targeted lymph node evaluation in colorectal cancer: A decade of progress!

Is PCR testing of sentinel lymph nodes ready for clinical application in breast cancer?

While the majority of breast cancer patients with histologically lymph node-negative cancers are cured by local therapy alone, approximately 25% will develop recurrent breast cancer and die of their disease in the absence of systemic adjuvant chemotherapy [1]. Cytotoxic chemotherapy markedly improves outcome for some of these patients. Assays that could better distinguish those nodenegative patients who are more likely to suffer distant recurrence could prove very useful in optimizing patient selection for chemotherapy. Technologies based on DNA microarray analysis using polymerase chain reaction (PCR) amplification seem like ideal candidates for the development of novel prognostic and predictive assays. The Oncotype DX TM test is a clinically validated, multigene assay performed on samples processed from primary invasive breast carcinomas. The assay provides a quantitative assessment of the likelihood of distant breast cancer recurrence in women with estrogen receptor-positive, node-negative disease, and also assesses the potential benefit from chemotherapy in these women [2]. A major strength of its 21-gene recurrence score is that it has been tested against outcomes data derived from the NSABP-B20 randomized trial in which cancer recurrence and survival is already known with several years of clinical follow-up. It seems likely that future assays will be developed using similar technology to address important clinical questions related to staging and cancer therapy.