Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2-Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2-Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial.

PURPOSE: SHR-A1811 is an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload. We assessed the safety, tolerability, antitumor activity, and pharmacokinetics of SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors. METHODS: This global, multi-center, first-in-human, phase I trial was conducted at 33 centers. Patients who had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies were enrolled. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg once every 3 weeks. The primary end points were dose-limiting toxicity, safety, and the recommended phase II dose. RESULTS: From September 7, 2020, to February 27, 2023, 307 patients who had undergone a median of three (IQR, 2-5) previous treatment regimens in the metastatic setting received SHR-A1811 treatment. As of data cutoff (February 28, 2023), one patient from the 6.4 mg/kg group experienced dose-limiting toxicities (pancytopenia and colitis). The most common grade 3 or higher adverse events (AEs) included decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. Serious AEs and deaths occurred in 70 (22.8%) and 13 (4.2%) patients, respectively. SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer, and 45.9% (39/85 with evaluable tumor responses) of the 98 nonbreast tumors. CONCLUSION: SHR-A1811 exhibited acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in heavily pretreated advanced solid tumors. The recommended phase II dose of 4.8 or 6.4 mg/kg was selected for various tumor types.

Metastatic colorectal cancer- third line therapy and beyond.

INTRODUCTION: The outcome of patients with metastatic colorectal cancer (mCRC) has improved significantly in the last few decades. Metastatic colorectal cancer is a highly heterogenous cancer. Beyond second line chemotherapy, treatment decisions are often based on molecular testing. METHOD: In this narrative review, we provide a comprehensive summary of data from key clinical trials and discuss how to integrate these agents into the current treatment landscape of metastatic colorectal cancer. EXPERT OPINION: In the era of precision medicine, molecular testing plays an increasingly important role in the management of mCRC. Efforts need to be made to target treatment based on molecular test results.

Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.

Background: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence. Objectives: To assess the impact of detecting methylated BCAT1/IKZF1 ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence. Design: A retrospective cohort study. Methods: The cohort included 180 patients (36 with recurrent CRC), who had undergone complete treatment and surveillance for a minimum of 3 years. Participant clinical details and ctDNA methylated BCAT1/IKZF1 results were compared between those with and without recurrence, and cox regression analysis assessed each factor on disease-free survival. Results: Clinical factors independently associated with reduced disease-free survival included nodal involvement (HR = 3.83, 95% CI 1.56-9.43, P = .003), M1 stage (HR = 4.41, 95% CI 1.18-16.45, P = .027), a resection margin less than 2 mm (HR = 4.60, 95% CI 1.19-17.76, P = .027), perineural involvement (HR = 2.50, 95% CI 1.01-6.17, P = .047) and distal tumors (HR = 3.13, 95% CI 1.07-9.18, P = .037). Methylated BCAT1/IKZF1 was detected in 51.7% (93/180) of pre-treatment plasma samples. When a positive ctDNA finding was considered in combination with these clinical prognostic factors, there was improved predictive power of recurrence for patients with perineural involvement (HR = 4.44, 95% CI 1.92-10.26, P < .001), and it marginally improved the predictive factor for M1 stage (HR = 7.59, 95% CI 2.30-25.07, P = .001) and distal tumors (HR = 5.04, 95% CI 1.88-13.49, P = .001). Conclusions: Nodal invasion, metastatic disease, distal tumor site, low resection margins and perineural invasion were associated with disease recurrence. Pre-treatment methylated ctDNA measurement can improve the predictive value for recurrence in a subset of patients, particularly those with perineural involvement. Registration: Australian and New Zealand Clinical Trials Registry #12611000318987.

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.

Mean-field model of synchronization for open-loop, swirl controlled thermoacoustic system.

Open-loop control is known to be an effective strategy for controlling self-excited periodic oscillations, known as thermoacoustic instability, in turbulent combustors. Here, we present experimental observations and a synchronization model for the suppression of thermoacoustic instability achieved by rotating the otherwise static swirler in a lab-scale turbulent combustor. Starting with the state of thermoacoustic instability in the combustor, we find that a progressive increase in the swirler rotation rate leads to a transition from the state of limit cycle oscillations to the low-amplitude aperiodic oscillations through a state of intermittency. To model such a transition while also quantifying the underlying synchronization characteristics, we extend the model of Dutta et al. [Phys. Rev. E 99, 032215 (2019)] by introducing a feedback between the ensemble of phase oscillators and the acoustic. The coupling strength in the model is determined by considering the effect of the acoustic and swirl frequencies. The link between the model and experimental results is quantitatively established by implementing an optimization algorithm for model parameter estimation. We show that the model is capable of replicating the bifurcation characteristics, nonlinear features of time series, probability density function, and amplitude spectrum of acoustic pressure and heat release rate fluctuations at various dynamical states observed during the transition to the state of suppression. Most importantly, we discuss the flame dynamics and demonstrate that the model without any spatial inputs qualitatively captures the characteristics of the spatiotemporal synchronization between the local heat release rate fluctuations and the acoustic pressure that underpins a transition to the state of suppression. As a result, the model emerges as a powerful tool for explaining and controlling instabilities in thermoacoustic and other extended fluid dynamical systems, where spatiotemporal interactions lead to rich dynamical phenomena.

Survival outcomes for patients with colorectal cancer with synchronous liver only metastasis.

BACKGROUND: Colorectal cancer with synchronous liver-only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear. METHODS: A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver-only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival. RESULTS: Data of over 5000 cases were analysed (n = 5244), 1420 cases had liver-only metastasis. There were a greater number of colon than rectal primaries (N = 1056 versus 364). Colonic resection was the preferred initial treatment for the colon cohort (60%). In the rectal cohort, 30% had upfront resection followed by 27% that had chemo-radiotherapy as 1st line therapy. For the colon cohort, there was an improved 5-year survival with surgical resection as initial treatment compared to chemotherapy (25% versus 9%, P < 0.001). In the rectal cohort, chemo-radiotherapy as the initial treatment was associated with an improved 5-year survival compared to surgery or chemotherapy (40% versus 26% versus 19%, P = 0.0015). Patients who were able to have liver resection had improved survival, with 50% surviving over 5 years compared to 12 months in the non-resected group (P < 0.001). Primary rectal KRAS wildtype patients who underwent liver resection and received Cetuximab had significantly worse outcomes compared to KRAS wildtype patients who did not (P = 0.0007). CONCLUSIONS: Where surgery is possible, resection of liver metastasis and primary tumour improved overall survival. Further research is required on the use of targeted treatments in patients undergoing liver resection.

Detection of methylated BCAT1 and IKZF1 after curative-intent treatment as a prognostic indicator for colorectal cancer recurrence.

BACKGROUND: The risk of recurrence after completion of curative-intent treatment of colorectal cancer (CRC) is hard to predict. Post-treatment assaying for circulating tumor DNA (ctDNA) is an encouraging approach for stratifying patients for therapy, but the prognostic value of this approach is less explored. This study aimed to determine if detection of methylated BCAT1 and IKZF1 following completion of initial treatment identified patients with a poorer recurrence-free survival (RFS). METHODS: 142 CRC stage I-III cases with at least 2 years of follow up (unless recurrence was evident sooner) and a methylated BCAT1/IKZF1 test result between 2 weeks and 12 months after completion of initial treatment were eligible for study inclusion. The association between BCAT1/IKZF1 and RFS was assessed by the log-rank (Mantel-Cox) method. Cox proportional hazard regression analysis was used for multivariable survival analysis. RESULTS: Thirty-three (23.2%) had recurrence at a median 1.6y (interquartile range: 0.8-2.4). Methylated BCAT1/IKZF1 was detected in 19 of the 142 patients (13.4%) and was associated with a significant risk of recurrence (hazard ratio [HR] 5.7, 95%CI: 1.9-17.3, p = 0.002). Three-year RFS for patients with or without detectable methylated BCAT1/IKZF1 was 56.5% and 83.3%, respectively. Multivariable analysis showed that detection of methylated BCAT1/IKZF1 (HR = 2.6, p = 0.049) and site of the primary tumor (HR = 4.2, p = 0.002) were the only significant prognostic indicators of poor RFS. CONCLUSIONS: BCAT1/IKZF1 methylation testing after curative-intent treatment is an independent prognostic indicator for RFS and identifies a subgroup at high risk. Personalized surveillance is warranted for patients with these ctDNA biomarkers detectable after curative-intent treatment.

Chemoradiotherapy with concurrent durvalumab for the palliative treatment of oligometastatic oesophageal and gastrooesophageal carcinoma with dysphagia: a single arm phase II clinical trial (PALEO, sponsored by the Australasian Gastro-Intestinal Trials Group).

BACKGROUND: Oesophageal and gastrooesophageal junction (GOJ) carcinoma frequently present with dysphagia and de novo metastatic disease. There is scope to improve treatment paradigms to both address symptoms and improve survival. One method is integrating immune checkpoint inhibition with novel treatment combinations. METHODS: PALEO is a single arm, phase II clinical trial in patients with previously untreated, oligometastatic or locoregionally advanced oesophageal or GOJ carcinoma and dysphagia. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG). Participants receive 2 weeks of therapy with concurrent hypofractionated radiotherapy of 30Gy in 10 fractions to the primary tumour, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2 and durvalumab 1500 mg q4 weekly, followed by durvalumab monotherapy continuing at 1500 mg q4weekly until disease progression, unacceptable toxicity or 24 months of therapy. A single metastasis is treated with stereotactic radiotherapy of 24Gy in 3 fractions in week 7. The trial primary endpoint is the progression free survival rate at 6 months. Secondary endpoints include duration of dysphagia relief, nutritional status change, quality of life, response rate, toxicity, progression free survival and overall survival. The tertiary endpoint is prediction of outcome based on biomarkers identified from patient serial blood samples collected pre- and post-radiotherapy. DISCUSSION: This unique investigator-initiated clinical trial is designed to simultaneously address the clinically relevant problems of dysphagia and distant disease control. The overarching aims are to improve patient nutrition, quality of life and survival with low toxicity therapy. AGITG PALEO is a multidisciplinary collaboration and will add to the understanding of the relationship between radiotherapy and the anti-tumour immune response. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12619001371189 , registered 8 October 2019.

Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma.

OBJECTIVES: Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer. METHODS: In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT). 3 + 3 design was used with nab-paclitaxel doses: 25 mg/m 2 (cohort 1), 50 mg/m 2 (cohort 2), 75 mg/m 2 (cohort 3), and 100 mg/m 2 (cohort 4). Primary endpoint was MTD. Secondary objectives were progression-free survival and overall survival. RESULTS: Fourteen patients were recruited. Median age was 69 years (range, 40-86). Grade 1/2 toxicities were nausea (93%), vomiting (54%), diarrhea (57%), and fatigue (69%). There were no dose limiting toxicities (DLT) in cohorts 1 to 3. In cohort 4, DLTs of febrile neutropenia and enterocolitis were observed in patient 1. Subsequent DLT of febrile neutropenia and enterocolitis occurred in patient 5 in the expanded cohort. Following chemoradiotherapy median progression-free survival was 4.7 months (95% confidence interval, 2.5-27.5) and median overall survival was 10.8 months (95% confidence interval, 6.37-25.2). CONCLUSIONS: Nab-paclitaxel and EBRT was well-tolerated at doses below 100 mg/m 2 . The MTD and recommended phase II study dose for nab-paclitaxel with EBRT is 75 mg/m 2 in this disease.

Immunotherapy use in oesophagogastric cancers-a review of the literature.

Cancers of the upper gastrointestinal tract are a leading cause of cancer-related death world-wide and historically have a poor prognosis. The incidence and histology of these cancers have varied temporally and geographically over the last three decades, with an emerging understanding of the differences in the molecular and genetic profiles across different subgroups. Management of oesophagogastric cancers is by a multidisciplinary team with utilisation of surgery, radiotherapy and systemic treatments in combinations where appropriate. Immune checkpoint inhibition (ICI) has drastically changed the treatment landscape of multiple solid malignancies in the last 5 years. In oesophagogastric cancer, clinical trials have only recently shown activity that is often associated with the molecular characteristics of these tumours, in particular PD-L1 scores or microsatellite instability (MSI-H). This review looks to present the pivotal trials in this space, discuss the complexities between trials that may explain the disparate results and assess the benefit ICI offers in the treatment landscape at present.

The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours.

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.

Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1.

Failure of colorectal cancer (CRC) treatment is due to residual disease, and its timely identification is critical for patient survival. Detecting CRC-associated mutations in patient circulating cell-free DNA is confounded by tumor mutation heterogeneity, requiring primary tumor sequencing to identify relevant mutations. In this study, we assessed BCAT1 and IKZF1 methylation levels to quantify circulating tumor DNA (ctDNA) and investigated whether this method can be used to assess tumor burden and efficacy of therapy. In 175 patients with CRC who were ctDNA-positive pretreatment, ctDNA levels were higher with advancing stage (P < 0.05) and correlated with tumor diameter (r = 0.35, P < 0.001) and volume (r = 0.58, P < 0.01). After completion of treatment (median of 70 days [IQR 49-109] after surgery, +/- radiotherapy, +/- chemotherapy), ctDNA levels were reduced in 98% (47/48) and were undetectable in 88% (42/48) of patients tested. For those with incomplete adjuvant chemotherapy after surgery, roughly half remained ctDNA-positive (11/21, 52.4%). The presence of ctDNA after treatment was associated with disease progression (HR 9.7, 95%CI 2.5-37.6) compared to no ctDNA. Assaying blood for ctDNA methylated in BCAT1/IKZF1 has the potential for identifying residual disease due to treatment failure, informing a potential need for therapy adjustment in advanced disease.

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

INTRODUCTION: Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice. AREAS COVERED: For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies, and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included journal publications, abstracts presented at major international oncology meetings, and ongoing clinical trials databases. EXPERT OPINION: Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm toward neoadjuvant therapy may improve resectability and survival rates; however, robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer.

BACKGROUND: Nivolumab improves disease control and survival in advanced NSCLC in patients with good performance status (PS), but there is limited data on its efficacy in patients with poor PS. AIM: Primary objective of the study was to evaluate the efficacy and safety of nivolumab and examine the influence of PS on outcomes. METHODS AND RESULTS: Retrospective analysis of patients treated with single-agent nivolumab for advanced NSCLC at a single institution was performed. Sixty-six patients treated with nivolumab were identified (33 male) with a median age of 68.5 years. Fifty-six (85%) patients were current or former smokers and 17 (26%) had brain metastasis. All patients had received prior chemotherapy, 39 (59%) patients received one and 27 (41%) had ≥2 prior lines of therapy. Median overall survival (OS) was 7.1 months (95%CI 3.61-11.3) in the overall study population. OS of patients with PS ≥2 at the start of treatment was 3.04 months (95%CI 1.64-7.36) as compared to 10.23 months (95%CI 7.06-18.9) with PS ≤1. The overall response rate was 7% (four patients had a partial response), 23 (40%) patients had stable disease; the overall disease control rate (partial response and stable disease) was 47%. Twenty-six (40%) patients had PS ≥2 at the start of treatment and 2 (8%) of these patients developed a partial response, 4 (15%) had stable disease; the overall disease control rate was 23%. Fourteen (58%) patients with PS ≥2 had disease progression at the time of first disease response evaluation. In the overall population, 20% of patients experienced grade ≥3 treatment-related adverse events (TRAEs), most commonly pneumonitis, hepatitis, and colitis. Fourteen TRAEs led to treatment discontinuation, 9 (23%) adverse events (AEs) in patients with PS ≤1 and 5 (19%) with PS ≥2. Fourteen (21%) patients died within 30 days of the last nivolumab treatment. CONCLUSION: There was no significant difference in toxicity leading to treatment discontinuation between the poor and good PS groups, but survival was shorter with poorer PS. PS appears to be an important prognostic factor and remains a relevant discriminator in the selection of treatment with immunotherapy for lung cancer.

Prognostic Differences of RAS Mutations: Results from the South Australian Metastatic Colorectal Registry.

BACKGROUND: Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome. OBJECTIVE: Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020. RESULTS: Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months. CONCLUSIONS: Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.

Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study).

AIMS: Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S-1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population. METHODS: The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21-day cycles of cisplatin (80 mg/m2 IV, day 1) plus capecitabine (1000 mg/m2 PO BD, days 1-14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1-3 were 10, 20, and 30 mg/m2 , respectively, in a 3 + 3 standard dose-escalation design. RESULTS: Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose-limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase-2 dose for IP paclitaxel was determined to be 30 mg/m2 . The 12-month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3-6.9). CONCLUSIONS: IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase-2 dose is 30 mg/m2 .

Regorafenib outcomes from the population based South Australian Metastatic Colorectal Cancer Registry.

AIM: Reviewing outcomes of regorafenib use in metastatic colorectal cancer using real-world data from the South Australian Metastatic Colorectal Cancer Registry. METHODS: A retrospective review of the characteristics and outcomes of patients who received regorafenib in the Registry up to December 2018. The registry started in February 2006. RESULTS: Fifty-three patients received regorafenib therapy since approved by the therapeutic goods administration in November 2013. The median age was 66 (range 34-82). 66% were male, 66% had stage IV disease at diagnosis, 53% had liver only involvement, whereas 13% had liver and lung disease and 6% had lung only involvement. 75% had left-sided primary. KRAS was available in 35/53 patients with 49% of them being WT. BRAF status was known in 8/53 with 25% of them having a mutated variant. MSI testing was known in 14 patients in whom 21% of them had MSI-High tumors. Prior lines of treatment received: one line 4%, two 9%, three 23%, four 26%, >four 37%. Prior biological use: bevacizumab 72%, anti-EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI, 2.8-3.8 years). Median survival from the start of regorafenib was 7.1 months (95% CI, 4.8-9.4 months) and the 12-month survival rate was 28%. CONCLUSION: The survival outcome for those patients from our population-based registry who access regorafenib is in keeping with reports from large, randomized trials. Thus, clinicians can quote local real world data when discussing efficacy and access to regorafenib therapy for mCRC patients.

Patterns of care and outcomes for gastric and gastro-oesophageal junction cancer in an Australian population.

BACKGROUND: A single state-wide upper gastrointestinal (GI) cancer video-linked multidisciplinary team (MDT) meeting guides management and evidence-based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro-oesophageal junction (GOJ) cancers. METHODS: Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage-specific survival outcomes were determined and analysed for each treatment modality. RESULTS: The study included 218 patients and at diagnosis 132 (61%) patients had stage I-III and 86 (39%) patients had stage IV disease. One hundred and ninety-five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty-six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6-NR), 22.8 (95% CI 20.4-43.2), and 6.0 months (95% CI 4.8-8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8-NR) for patients who underwent surgery alone. CONCLUSION: Treatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence-based practice. However, as most patients continue to present with late-stage disease, longer-term survival remains poor.

Predicting chemotherapy-induced menopause using baseline and post-chemotherapy anti-Müllerian hormone levels: Results of a pilot study.

BACKGROUND: Chemotherapy can cause premature menopause which may result in adverse effects such as fertility loss, osteoporosis, cardiovascular disease and menopausal symptoms. It is thus very important that women are provided with accurate information regarding their risk of premature menopause as a consequence of proposed chemotherapy. Unfortunately, at present there are no reliable tools which can be applied in clinical practice to estimate the risk of premature menopause in women undergoing chemotherapy, beyond age of the patient and form of chemotherapy utilized. AIM: This was a pilot study to determine whether AMH levels pre and during chemotherapy are able to predict for chemotherapy induced menopause, and to assess quality of life and menopausal symptoms. METHODS AND RESULTS: Premenopausal women between 18 to 45 who were planned to undergo gonadotoxic chemotherapy with curative intent for either breast cancer or haematologic malignancy were recruited from a single centre. AMH, FSH, LH and oestradiol levels were recorded prior to commencement of therapy, during and following completion of chemotherapy. Menstrual status, menopausal symptoms and quality of life data were collected at baseline and during follow-up. Twenty two women were recruited. The baseline AMH was higher in women who regained menses post-chemotherapy (median 23.1 vs 9.9 pM (P = .06). Menopausal symptoms were significantly higher at 1 year post diagnosis than at baseline however quality of life was similar. CONCLUSION: AMH may be useful for predicting chemotherapy induced menopause. Further research is still required to determine the place of such testing for patient counselling and management.