Uncertainty and the unmet informational needs of patients with cancer of unknown primary (CUP): a cross-sectional multi-site study.

OBJECTIVE: This study aimed to determine the healthcare experiences, quality of life, and psychosocial needs of patients with cancer of unknown primary (CUP) early after diagnosis; comparing their experiences to patients with advanced cancer of a known primary (non-CUP control patients) and published general population reference data where available. METHODS: This study was a cross-sectional, multi-site study comparing CUP patients (n = 139) compared to non-CUP controls (n = 45). Demographic, clinical information and patient-reported outcome questionnaire data were collected at baseline. RESULTS: Differences in healthcare experienced were found between CUP and non-CUP controls with CUP patients reporting higher scores for unmet medical communication/information needs compared with non-CUP control patients (p = 0.013) as well as greater uncertainty in illness (p = 0.042). Whilst no differences were found between CUP and non-CUP controls on the EORTC and PROMIS measures, of those that 'received written information about your cancer…' and asked '…how useful was it?' fewer CUP patients reported finding the information useful 40% vs 61%, and more were likely to not have received written information at all 59% vs 32%; (p = 0.002). Additionally, of those that found information about their cancer online, fewer patients with CUP reported finding it useful 32% vs 48% control patients (p = 0.005). CONCLUSIONS: CUP patients have unmet medical communication/information needs and greater uncertainty in illness but do not differ in health-related quality of life domains compared to patients with advanced cancer of a known primary.

MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG).

BACKGROUND: Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a "lighter" treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. METHODS/DESIGN: MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. DISCUSSION: MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018.

Hepatitis B screening before rituximab therapy: a multicentre South Australian study of adherence.

BACKGROUND: International guidelines recommend screening for hepatitis B virus (HBV) infection prior to administration of rituximab, due to high risk of HBV reactivation in at-risk patients. AIMS: To determine: (i) adherence to the South Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation. METHODS: All patients commenced on rituximab at the six major SA public hospitals during a 12-month period were included in the study. Adherence was assessed by documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a minimum of 6 months following rituximab initiation. RESULTS: Four hundred and thirty eight patients were included in the study. The main indication for rituximab therapy was haematological malignancy (76.0%). Two hundred and nine (47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified prevalence of at-risk cases (either HBsAg- or HBcAb-positive) within the study population was 4.6% (20/438 cases). One case of HBV reactivation was identified, but none led to acute liver failure, transplantation or death. CONCLUSIONS: Poor adherence to HBV screening protocols suggests the need for targeted clinician education and system redesign. While the rate of reactivation was low, the prevalence of at-risk patients in this population was high and justifies further initiatives to increase adherence rates to HBV screening pre-rituximab.

Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers.

Immune checkpoint inhibitors (ICI) are an important development in the treatment of advanced cancer. A substantial proportion of patients treated with ICI do not respond, and additionally patients discontinue treatment due to adverse effects. While many novel biological markers related to the specific mechanisms of ICI actions have been investigated, there has also been considerable research to identify routinely available blood and clinical markers that may predict response to ICI therapy. If validated, these markers have the advantage of being easily integrated into clinical use for nominal expense. Several markers have shown promise, including baseline and post-treatment changes in leucocyte counts, lactate dehydrogenase and C-reactive protein. While promising, the results between studies have been inconsistent due to small sample sizes, follow-up time and variability in the assessed markers. To date, research on routinely available blood and clinical markers has focussed primarily on ICI use in melanoma, the use of ipilimumab and on univariate associations, but preliminary evidence is emerging for other cancer types, other ICIs and for combining markers in multivariable clinical prediction models.

ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours.

BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are "wild type"). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a "quadruple wild type" tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. METHODS AND DESIGN: ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with "quadruple wild type" or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. DISCUSSION: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the "quadruple wild type", which may 'superselect' for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808 , registered 16 August 2012.

Is self-management feasible and acceptable for addressing nutrition and physical activity needs of cancer survivors?

BACKGROUND: Self-management is recommended for patients with chronic conditions, but its use with cancer survivors is underexplored. Optimal strategies for achieving lifestyle changes in cancer survivors are not known. OBJECTIVE: We aimed to determine feasibility, acceptability and preliminary efficacy of self-management-based nutrition and physical activity interventions for cancer survivors. DESIGN, SETTING AND PARTICIPANTS: Adult survivors (n = 25) during (Group 1 , n = 11) or post (Group 2, n = 14)-curative chemotherapy for solid tumours, most (n = 20, 80%) with breast cancer, were recruited prospectively from a single clinical centre. INTERVENTION: The Flinders Living Well Self-Management Program, a generic self-management care planning programme, was utilized to establish patient-led nutrition and exercise goals within a tailored 12-week intervention. Fortnightly progress reviews occurred with assessments at baseline, 6 and 12 weeks. RESULTS: Most participants (84%) found the intervention acceptable/very acceptable. Both groups showed a trend towards significant improvement in the self-management capability 'knowledge about changing risk factors' (P = 0.047); Group 2 showed a trend towards significantly improved 'psychological impacts' (P = 0.007). Goal ratings improved for both groups (P = 0.001). Quality of life improved for both groups for emotional functioning (P = 0.03). Physical functioning improved for Group 2 (P = 0.05); however, most symptom domains worsened for Group 1, as expected given their treatment stage. DISCUSSION AND CONCLUSIONS: Self-management interventions are feasible for this population. In particular, building self-management capacity during the active phase of patients' cancer treatment provides health and psychosocial benefits. Larger randomized controlled trials are required to further determine efficacy. Further translational research is also needed to determine acceptability,feasibility, enablers and barriers for clinicians embedding this approach into routine cancer survivorship care.

Primary site and treatment impact in unresectable metastatic colorectal cancer.

INTRODUCTION: Colorectal cancer is a heterogenous disease, with various clinical and molecular subtypes related to the primary site (left versus right colon) of the original tumor. Primary colon tumor side is both a prognostic and predictive marker in metastatic colorectal cancer. AREAS COVERED: There is an increasing body of evidence for how primary site may impact treatment decisions in metastatic colorectal cancer. We reviewed the evidence for its prognostic and predictive value. EXPERT OPINION: Primary site is a prognostic marker in metastatic colorectal cancer, with right colon tumors being associated with more aggressive disease behavior and poorer outcomes. Primary site also appears to predict for outcomes to various treatments, in particular anti-EGFR antibodies. As our understanding and testing of the molecular and biological differences within colorectal cancer increases beyond primary site, this should be integrated into the current treatment algorithm to ensure an individualized patient-centered approach to care.

Immune checkpoint inhibitor-associated hemophagocytic lymphohistiocytosis in a patient with chronic lymphocytic leukemia.

Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of immune checkpoint inhibitor therapy. A 55-year-old male with stable chronic lymphocytic leukemia presented with fevers and symptomatic anaemia after nine cycles of nivolumab for metastatic melanoma. Investigations were consistent with autoimmune haemolytic anemia and corticosteroids were initiated. Thrombocytopenia and elevated liver enzymes without evidence of chronic lymphocytic leukaemia transformation was present. Ferritin was elevated, and thus HLH was considered and subsequently confirmed on a bone marrow biopsy. Corticosteroid monotherapy was continued, with resolution of fevers and improvement in cytopenias and liver enzymes. A six month corticosteroid tapering regimen was initiated, and he remains in HLH remission. This case highlights the importance of prompt recognition of immune checkpoint inhibitor-related HLH in patients with concurrent haematological malignancy.

A 55-year-old man had skin cancer and treatment was started. He also had a blood cancer around the same time that was not causing any problems. The skin cancer treatment started to cause problems many weeks later. His immune system started to react and become more active and so his liver started to suffer. The treatment for his skin cancer was stopped and steroids were started, which eventually improved his condition. These treatments for skin cancer can activate the immune system, but to this extent is not very common. It is important to know that it is possible and needs to be actioned early.

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis.

OBJECTIVE: To further investigate the effect of sunitinib, which is currently a standard of care for the treatment of metastatic renal cell carcinoma (mRCC), in patients with severe renal impairment or those undergoing dialysis. PATIENTS AND METHODS: Clinical databases were used to identify all patients with mRCC treated with sunitinib in seven institutions internationally. Databases were searched to identify only those patients with an estimated glomerular filtration rate of < 30 mL/min/1.73 m² or those who had end-stage renal disease requiring dialysis. Baseline characteristics, adverse event data, response and progression-free survival were recorded. RESULTS: Nineteen patients met the inclusion criteria, 10 of whom were undergoing haemodialysis. Of the nine non-dialysis-dependent patients at drug initiation, the median estimated glomerular filtration rate was 27 mL/min/1.73 m² (range 23-29). Baseline characteristics included a median age of 61 years (range 44-77); 17 patients had a Karnofsky performance status of >80; eight patients had more than two metastatic sites and 17 had undergone prior nephrectomy. The estimated median progression-free survival of this cohort was 43 weeks (range 7 to 158+) and progression has not yet been reached in six patients. Partial response or stable disease was observed as best response in 15 patients. The most common treatment-related adverse events included fatigue, diarrhoea, hand-foot skin reaction (HFSR), nausea and vomiting and rash. Grade three treatment-related adverse events including fatigue (seven patients), HFSR (two patients), diarrhoea (one patient), rash (one patient) and stomatitis (one patient) occurred in a total of 12 patients. Only one patient experienced a grade four adverse event (HFSR). Only diarrhoea (P = 0.0002), HFSR (P < 0.0001) and neutropenia (P = 0.001) were more common in patients undergoing haemodialysis compared with non-dialysis-dependent patients. Four of the non-dialysis dependent patients started at a dose of 50 mg compared with three of the patients undergoing haemodialysis. However five and two of the patients undergoing haemodialysis started at doses of 37.5 mg and 25 mg daily, respectively, compared with four and one of the non-dialysis-dependent patients. All patients took sunitinib for 4 out of every 6 weeks. Dose reductions during treatment were performed in eight patients but only one patient required discontinuation of treatment. CONCLUSION: These data suggest that patients with severe renal impairment or end-stage renal disease on haemodialysis can be safely treated with sunitinib at doses of 25-50 mg daily for 4 weeks followed by a 2-week break. The observed efficacy of therapy is similar to that reported in patients with normal renal function. These preliminary results warrant confirmation in a larger cohort of patients.

Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab.

BACKGROUND: Preliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs. METHODS: The study pooled data from patients with NSCLC in the randomized trials OAK and POPLAR (atezolizumab vs docetaxel; n=1464), and single-arm atezolizumab trials BIRCH and FIR (n=797). The association between ETS (≥10% decrease in pretreatment sum-of-longest diameters of target-lesions at 6 weeks) and overall survival (OS), progression-free survival (PFS), time to deterioration (TDD) in health-related quality-of-life (HRQoL) and physical function (PF) was assessed using Cox proportional hazard analysis. RESULTS: ETS occurred in 20% of atezolizumab-treated patients with NSCLC within OAK and POPLAR and was associated with highly favorable OS (HR 0.33, p<0.001), PFS (HR 0.31, p<0.001), TDD in HRQoL (HR 0.73, p=0.01) and PF (HR 0.52, p<0.001). The results were replicated in the BIRCH and FIR data. Atezolizumab-treated patients achieving ETS had markedly improved OS compared with docetaxel-treated patients achieving ETS (24-month OS 55% vs 32%); PFS was also markedly improved (24-month PFS 31% vs 4%). In contrast, for patients not achieving ETS, atezolizumab-treatment was associated with more modest OS (24-month OS 23% vs 20%) and PFS (24-month PFS 3% vs 1%) improvement compared with docetaxel. Overall, the effect size for ETS within the atezolizumab-treated patients was significantly greater than that in the docetaxel-treated patients (P(interaction)=0.002 for OS and P(interaction)<0.001 for PFS). CONCLUSIONS: ETS is an easily measurable biomarker, predictive of highly favorable survival and patient-reported outcomes with atezolizumab treatment for advanced NSCLC. Further, ETS identifies patients with significantly greater treatment benefit for ICI therapy.

Rechallenge with Anti-EGFR Therapy in Metastatic Colorectal Cancer (mCRC): Results from South Australia mCRC Registry.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) are today increasingly used in the first- or second-line setting for RAS wild-type metastatic colorectal cancer (CRC) patients. Following progression beyond third- or fourth-line therapy, some patients are unsuitable for further chemotherapy because of poor performance status or patient choice. However, a significant number of patients are still candidates for further therapy despite limited standard options being available. The role of rechallenge with anti-EGFR therapy, particularly in patients who had previously responded, is often considered, but there is limited evidence in the literature to support such a strategy. OBJECTIVE: This retrospective study aims to review the outcome of metastatic CRC patients who had anti-EGFR rechallenge. PATIENTS AND METHODS: Patients who had been rechallenged with anti-EGFR therapy were identified from the South Australian metastatic CRC database. Patient characteristics were recorded and tumor response was retrospectively assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Kaplan-Meier analysis was used to assess progression free survival (PFS) for each rechallenge and overall survival (OS). RESULTS: Twenty-two patients were eligible for inclusion in this analysis. Disease control rate (stable disease and partial response) was 45.4% (ten patients) for patients who received rechallenge anti-EGFR. Seven patients received a second rechallenge and disease control rate was 28.6% (two patients). The median interval time between initial anti-EGFR therapy and rechallenge was 13.5 months. The median PFS after rechallenge 1 was 4.1 months and after rechallenge 2 was 3.5 months. The median OS was 7.7 months from date of rechallenge. CONCLUSIONS: Anti-EGFR rechallenge provides clinical benefit in patients with RAS wild-type metastatic CRC.

Monitoring TNM stage of female breast cancer and survival across the South Australian population, with national and international TNM benchmarking: A population-based cohort study.

OBJECTIVE: Using linked cancer registry and administrative data to monitor, tumour, node and metastases (TNM) stage and survival from female breast cancer in Australia. METHOD: Analysis of 2000-2014 diagnoses with linked population-based data to investigate: (1) sociodemographic predictors of advanced stage (stages III and IV), using unadjusted and adjusted logistic regression; and (2) sociodemographic factors and stage as predictors of breast cancer survival using competing risk regression. DESIGN: Population-based registry cohort. SETTING AND PARTICIPANTS: 14 759 South Australian women diagnosed in 2000-2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Stage and survival. RESULTS: At diagnosis, 46% of women were classified as stage I, 39% as stage II, 12% as stage III and 4% as stage IV. After adjusting for sociodemographic factors, advanced stage was more common: (1) for ages <50 years; and although not statistically significant, for ages 80+ years; and (2) in women from socioeconomically disadvantaged areas. Compared with 2000-2004 diagnoses, stage and sociodemographic adjusted risks (sub-HRs (SHRs)) of breast cancer death were lower in 2005-2009 (SHR 0.75, 95% CI 0.67 to 0.83) and 2010-2015 (SHR 0.57, 95% CI 0.48 to 0.67). Compared with stage I, the SHR was 3.87 (95% CI 3.32 to 4.53) for stage II, 10.87 (95% CI 9.22 to 12.81) for stage III, and 41.97 (95% CI 34.78 to 50.65) for stage IV. Women aged 70+ years at diagnosis and those living in the most socioeconomically disadvantaged areas were at elevated risk of breast cancer death, independent of stage and sociodemographic factors. CONCLUSIONS: Stage varied by age, diagnostic period and socioeconomic status, and was a stronger predictor of survival than other statistically significant sociodemographic predictors. Achieving earlier diagnosis outside the original BreastScreen target of 50-69 years (as applying <2014) and in residents of socioeconomically disadvantaged areas likely would increase cancer survival at a population level.

Prognostic model of survival outcomes in non-small cell lung cancer patients initiated on afatinib: pooled analysis of clinical trial data.

OBJECTIVE: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer (NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been evaluated. METHODS: A prognostic tool for overall survival (OS)/ progression free survival (PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6 (n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1 (n = 390) and LUX-Lung 2 (n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment. RESULTS: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group. CONCLUSIONS: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.

Patterns of care in Jehovah's Witnesses patients with solid tumours and lymphoma.

BACKGROUND: Supportive care of Jehovah's Witnesses (JWs) diagnosed with cancer can be challenging, as they do not accept red blood cell (RBC) transfusions. AIM: The study was designed to determine treatment preferences and pattern of care offered to JWs diagnosed with cancer and its impact on cancer management. METHODS AND RESULTS: A retrospective cohort study of JWs with solid malignancies or lymphoma in our institution between 2005 and 2015 was conducted. Survival statistics were estimated using Kaplan Meier survival curves and Cox proportional regression model. A total of 63 JWs were identified with a median age of 70 years. At diagnosis, 34% (n = 22) had anaemia. All 63 declined RBC transfusion, including 19 patients who later developed transfusion threshold during anti-cancer treatment. Forty-three percent (n = 27) JWs had advanced (stage 4) disease, and 76% (n = 48) had Eastern Cooperative Oncology Group of 0 to 1. JWs were willing to accept surgery and radiation rather than chemotherapy. Treatment was deemed to be suboptimal in 22% (n = 14) JWs due to early treatment discontinuation, administration of non-standard chemotherapy regimen, or dose reduction due to anaemia and denial of blood transfusion. Twenty-seven percent (n = 17) received hematopoietic growth factors (erythropoiesis-stimulating agents and pegfilgrastim). There was no mortality directly attributed to anaemia or refusal of blood transfusion in the entire cohort. CONCLUSION: Jehovah's Witnesses declined RBC transfusion at diagnosis and during cancer therapy even if medically indicated. Management pathways need to be prospectively defined for this group of patients.

Phase II study of celecoxib with docetaxel chemoradiotherapy followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer.

TITLE: Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer. INTRODUCTION: Concurrent CRT has been associated with improvement in absolute 5-year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase-2 inhibition may increase the efficacy of CRT. METHODS: Patients were treated with CRT (weekly docetaxel at 30 mg/m2 over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m2 given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response. RESULTS: Twenty-four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression-free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance. CONCLUSIONS: The activity of this regimen has been demonstrated. Treatment-related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

INTRODUCTION: Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Targeted therapy for metastatic colorectal cancer.

INTRODUCTION: Outcomes in metastatic colorectal cancer are improving, with better understanding and use of targeted therapies. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) agents, the relevance of primary tumor location and novel subgroups such as BRAF mutated, HER2 amplified, and mismatch-repair-deficient cancers. Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for metastatic colorectal cancer (mCRC). The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumors. Clinically, mCRC can be divided into subgroups based on RAS, BRAF, HER2, and MMR status, each of which have distinct treatment pathways.

Observation of "complete clinical response" in rectal cancer after neoadjuvant chemoradiation: The Flinders experience.

AIM: Observation with close follow-up ("watch and wait") is a recognized treatment option in patients who achieve a complete clinical response to long course chemoradiotherapy. This review of a prospective database aims to evaluate the clinical outcomes among patients with a complete clinical response managed with observation. METHODS: A prospective study of 32 patients who achieved a complete clinical response was undertaken. The primary outcomes measured were overall and recurrence-free survival, and rate of organ preservation in patients who deferred immediate surgery. RESULTS: Seven patients developed local regrowth over a median follow-up period of 38 months (range, 9-91 months). Median time to detection was 12 months. All seven underwent salvage surgery with complete surgical clearance. One patient developed combined local and systemic recurrence following a low anterior resection. Organ preservation was possible in 25 (78%) patients who sustained a complete clinical response with no evidence of local regrowth or disease recurrence. Among the patients who sustained a complete response, two developed isolated systemic disease. Overall and recurrence-free survival was 95.7% and 87.0%, respectively. CONCLUSION: The majority of patients with rectal cancer who achieved a complete clinical response after chemoradiotherapy and managed with a "watch and wait" approach preserved their rectum and did not develop cancer relapse. Salvage surgery was achieved in all patients who developed local regrowth. The study supports a period of observation in rectal cancer patients who achieve a complete clinical response.

Multimodal Anti-tumor Approaches Combined with Immunotherapy to Overcome Tumor Resistance in Esophageal and Gastric Cancer.

Upper gastrointestinal malignancies are associated with a high disease burden worldwide, and esophageal and gastric cancers represent the most common entities. Given a lack of early characteristic symptoms and potent screening instruments, the majority of patients present with advanced disease at the time of diagnosis. Complete surgical resection is a first-line curative option, and multimodal approaches involving chemotherapy and radiotherapy further improve patient prognosis. However, response to standard adjuvant and neoadjuvant treatments remains low, and new strategies are warranted to increase tumor control rates. Immunotherapy is emerging in various cancer entities and may be successfully combined with standard therapeutic regimens to improve patient outcome. For the purpose of this review we aimed to assess combined approaches of immunotherapy and standard treatment options such as chemotherapy, radiotherapy and surgery. Current trials evaluating multimodal approaches with immunotherapy in esophageal and gastric cancer are evaluated.