12016 Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a significant and persisting toxicity of anticancer treatments, impacting dose delivery and quality of life. There is a lack of consensus on the optimal method of CIPN assessment in clinical settings. This study compared the validity and responsiveness of patient reported outcome measures (PROMs) against neurological, neurophysiological and sensory assessment approaches of CIPN. Methods: A multi-centre dual study design evaluated patients treated with neurotoxic chemotherapy across two cohorts: patients commencing treatment assessed prospectively and patients who completed treatment assessed cross-sectionally. CIPN was assessed via PROMs (EORTC-CIPN20, FACT/GOG-Ntx, PRO-CTCAE), neurological and neurophysiological assessment (Total Neuropathy Score, sural and tibial compound nerve amplitudes) and sensory functional measures (Grating orientation, Von Frey monofilament and 2-Point discrimination tasks). Convergent and known-groups validity were assessed cross-sectionally following treatment completion and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between high and low CIPN symptom reporters. Results: A total of 1,033 patients were recruited, incorporating 1,623 assessments. PROMs demonstrated superior ability to identify CIPN (convergent validity; α = 0.75-0.85, all P < 0.001), to discriminate between CIPN severity (known-groups validity; all P < 0.001) and to detect changes in CIPN development (responsiveness; Cohen’s d = 0.65-0.83) compared to neurological, neurophysiological and sensory assessment approaches. These other measures did not achieve threshold for convergent validity (α < 0.7). and did not demonstrate acceptable responsiveness (Cohen’s d < 0.5). Neurological, neurophysiological, and sensory outcome measures were significantly impaired in patients who were high CIPN symptom reporters compared to low (all P < 0.05). Conclusions: PROMs represent a valid method of CIPN assessment, with preferential measurement properties over other approaches to assessing neuropathy. Adoption of PROMs in clinical practice will allow for accurate representation and early recognition of CIPN, leading to reduced long term morbidity in this key long-term toxicity in cancer survivors.

e17554 Background: Ovarian cancer (OC) is a heterogenous group of malignancies, most of which are rare. Data on patterns of care and survival of the most-rare sub-groups of OC (incidence rates < 6 per 100,000) in the real-world setting is limited. This study aims to describe patterns of care and overall survival (OS) for women with rare ovarian cancers in Australia. Methods: Clinical data were sourced from the NGOR and assessed for accuracy and completeness. High grade serous and endometrioid OC subtypes were excluded. Due to incompleteness of survival follow-up data, 3-year OS was only calculated for the state of Victoria. Results: Data on 2812 women with newly diagnosed OC from 2017-2023 within NGOR were collected and 716 women were subsequently identified with rare subtypes of OC. The 5 sub-types with the highest incidences were clear cell (n = 168, 23.4%), mucinous (n=151, 21.1%), adult granulosa cell (n=111, 15.5%), low grade serous (n=98, 13.7%) and carcinosarcoma (n=59, 8.2%). A further 23 additional rare subtypes included germ cell tumours and sex cord stromal tumours. The median follow-up time was 2.6 years and median age at diagnosis was 55 years. Most women had an ECOG 0-1 performance status (n=551, 77.0%). The primary treatment modality was surgery only (n=360, 50%), followed by surgery and systemic therapy (n = 317, 44.2%), systemic therapy only (n=28, 3.9%) and no treatment (n=11, 1.5%). Most women were discussed at a multi-disciplinary meeting (n=701, 97.9%). The diagnosis was confirmed on histology for all women. The 30-day post-operative adverse events (Clavien-Dindo >III severity) was 3.6 % (n=26), with the highest rate of post-operative events in the carcinosarcoma group of 12% (n=6). Using Fisher’s exact test across the 5 most common sub-types described above, there were significant differences in treatment modalities (p<0.001), rates of 30-day post-operative events (p=0.002), age adjusted charlson comorbidity index (p<0.001) and metropolitan versus remote regional status (p=0.007) between the sub-types. Survival at 3 years for these five sub-types of rare OC within the state of Victoria are summarised in the table. The highest 3-year OS was in adult granulosa and low grade serous sub-types. Conclusions: This is a large, real-world analysis of patterns of care and survival for women with rare sub-types of OC. Combining data with international sites will likely further enhance research on patterns of care and outcomes for women with rare OC. [Table: see text]

A list of copy number alterations, rearrangements and short variants detected by Foundation Medicine NGS

5526 Background: Gynecological (gyne) cancers are highly diverse with distinct sites of origin and histological subtypes that can limit development of evidence-based therapies. Comprehensive genomic profiling (CGP) has an increasing role in characterizing clinically relevant molecular subsets and in identifying actionable biomarkers with potential to guide therapy selection. Methods: MoST (ACTRN12616000908437) is an Australia-wide precision oncology program for adult patients (pts) with advanced cancers and limited treatment options. Tumor specimens are analysed by CGP and genomic results tiered by the level of evidence supporting matched therapies (https://topograph.info). Pts are followed for subsequent treatment and survival. Here, we present data for the MoST gyne cancer cohort. Results: Between Sept 2016 and Oct 2022, 533 gyne tumors were sequenced, with included pts having a minimum 4 months (mo) follow-up. Key histotypes included: ovarian serous (n=162) and non-serous (n=46) epithelial tumors; uterine carcinomas (n=99) and sarcomas (n=108); cervical carcinomas (n=51); germ cell and sex-cord stromal tumors (n=18); carcinosarcomas (n=33); and vulva/vaginal tumors (n=16). The median number of reported variants was 3 (IQR 2-5) and tumor mutational burden 3.1 mut/Mb (IQR 1.3—5.5, Range 0—284); 9 (2%) tumors were microsatellite unstable; and 22 (4%) had high level loss-of-heterozygosity (confirmed on validated genome-wide assays). The most common pathways involved in this pan-gyne cohort were: p53 (n=287, 54%), PI3K/AKT (n=227, 43%), cell cycle (n=182, 34%), and mitogen-activated protein kinase (n=91, 17%). Pathogenic mutations in BRCA1/2 were identified in 29 tumors (5%; 18 in ovarian serous cancers), whereas 81 tumors (15%) had alterations in other homologous recombination genes, most commonly uterine sarcomas (n=32, 30%). Actionable genomic biomarkers matched to a clinically active treatment (TOPOGRAPH tier 1-3) were identified in 207 (39%) tumors. In 19 pts (3.5%) who received Tier 1-3 matched therapy after CGP, a trend towards longer survival was observed (median OS 22.3 mo, 95% CI 17.3 to not reached) compared to those receiving unmatched therapy (n=65, median OS 14.9 mo, 10.2 to 22.1, p=0.052) following CGP. No OS difference was seen in pts who received matched investigational therapy (Tier 3B/4, n=31, median OS 17.0 mo, 8.1 to NR) versus only unmatched therapy (n=118, median OS 14.0 mo, 11.3 to 22.5; HR 0.97, 0.57 to 1.64; p=0.91). Conclusions: CGP identified actionable genomic results in nearly half of advanced gyne cancers, with enrichment in particular histotypes that supports testing above current standard of care. Trends in prolonged OS with subsequent matched therapies may be better realized with earlier testing and improved drug/clinical trial access.

OBJECTIVE:Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC.RESULTS:Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival.METHODS:224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing.CONCLUSIONS:This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit.

Internal Medicine JournalVolume 34, Issue 5 p. 298-299 Prevention of hepatotoxicity but loss of antimelanoma effect with combined fotemustine and anti-oxidant treatment G. J. M. Webster, G. J. M. Webster 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 J. Kurtovic, J. Kurtovic 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 I. Singh-Grewal, I. Singh-Grewal 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 M. Friedlander, M. Friedlander 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 2 S. M. Riordan, S. M. Riordan 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 G. J. M. Webster, G. J. M. Webster 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 J. Kurtovic, J. Kurtovic 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 I. Singh-Grewal, I. Singh-Grewal 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 M. Friedlander, M. Friedlander 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 2 S. M. Riordan, S. M. Riordan 1 Gastrointestinal and Liver Unit and 2Institute of Oncology The Prince of Wales Hospital and University of New South Wales Sydney, New South Wales AustraliaSearch for more papers by this author 1 First published: 19 May 2004 https://doi.org/10.1111/j.1444-0903.2004.00598.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume34, Issue5May 2004Pages 298-299 RelatedInformation

OBJECTIVE: Individuals with chronic hepatitis C who are anti-HBc positive may carry an occult hepatitis B virus (HBV) infection that can affect their response to antiviral therapy. METHODS: In this study the prevalence of anti-HBc and HBV–DNA positivity was assessed in the serum and liver of 285 HCV–RNA-positive subjects treated with interferon-α at 5 mU/day for 12 months. The response to interferon (normal ALT and undetectable serum HCV–RNA) was evaluated at three different endpoints: 1) after 6 months; 2) at the end of treatment; and 3) 6 months after interferon discontinuation. RESULTS: Ninety individuals were anti-HBc positive (32%), 2 of these were HBV–DNA positive in serum and 7 in liver (8%). None of the anti-HBc-negative individuals was HBV–DNA positive in serum or liver. The prevalence of cirrhosis was greater in the anti-HBc-positive group than in the anti-HBc-negative group (p < 0.05), whereas HCV–RNA levels were lower. Anti-HBc-positive individuals had a lower response rate to interferon at 6 months and at the end of treatment as compared to anti-HBc-negative subjects (respectively 42% vs 66%, p < 0.01; and 32% vs 57%, p < 0.01). No difference between the two groups in terms of sustained response was detected 6 months after interferon discontinuation. CONCLUSIONS: The prevalence of anti-HBc is high among HCV-positive individuals. HCV-positive individuals who are anti-HBc positive have: 1) a higher prevalence of cirrhosis; 2) lower HCV–RNA levels; and 3) an impaired ability to respond to interferon treatment.

A major impediment to the wider application of clinical liver transplantation is the paucity of acceptable organs. Most centers refuse organs that come from donors who are hepatitis B core antibody positive because of a fear of transmission of hepatitis B virus (HBV) infection to the recipient. The risk related to the use of such donor organs has never been assessed in an ordered manner. The presence or absence of polymerase chain reaction detectable HBV-DNA in liver tissue of individuals undergoing liver biopsy for clinical reasons was assessed in 133 consecutive patients. A total of 8.2% of these livers resulted positive for HBV-DNA; interestingly the rate was higher among those who were hepatitis B surface antibody positive (12.5%) as compared to those without detectable hepatitis B surface antibody (5.7%). These data provide measures of putative risk for HBV infection in liver transplant recipients associated with the use of organs obtained from a hepatitis B core antibody positive donor.

Treatment of chronic hepatitis B virus (HBV) infection in an individual with periarteritis nodosum is described. A combination of famciclovir, granulocyte macrophage colony stimulating factor (GM-CSF) and interferon alpha 2b was utilized. The periarteritis, but not the HBV infection, responded to immunosuppressive therapy consisting of cyclophosphamide and glucocorticoids. Moreover, the patient failed to clear this HBV infection, despite a full year of interferon therapy at 5 MU daily. With the addition of famciclovir and GM-CSF, the HBV infection rapidly resolved and he converted from HBsAg and eAg positive to HBsAb and eAb positive. No exacerbation of his periarteritis nodosum occurred during the course of his antiviral therapy.