Rohit Joshi

Left and right ventricular effects of anthracycline and trastuzumab chemotherapy: A prospective study using novel cardiac imaging and biochemical markers

This article appeared in a journal published by Elsevier. Under Elseviers copyright, mandated authors are not permitted to make work available in an institutional repository.

Colorectal cancer treatment and survival: the experience of major public hospitals in south Australia over three decades.

BACKGROUND Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. MATERIALS AND METHODS Kaplan-Meier product- limit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. RESULTS Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. CONCLUSIONS We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Early cardiac changes following anthracycline chemotherapy in breast cancer: a prospective multi-centre study using advanced cardiac imaging and biochemical markers

Summary This prospective study is designed to identify novel ima- ging (utilizing cardiovascular magnetic resonance and advance echocardiography) and biochemical markers to detect early, sub-clinical cardiotoxicity following chemotherapy. Background Cardiac toxicity is an important long term side effect of anthracyline chemotherapy. We hypothesized that novel cardiovascular magnetic resonance (CMR) and echocar- diographic markers of myocardial function, oedema, and necrosis can detect early, subclinical cardiac toxicity in patients receiving anthracycline therapy for breast cancer. recovery fast-spin echo sequence (short-TI inversion recovery) was used in 3 short-axis views of the left ven- tricle. For assessment of myocardial oedema, the ratio of mean signal intensity (SI) of the myocardium was com- pared to that of skeletal muscle. Results In the study patients, the mean CMR LV end-systolic volume index (LVESVI) increased from baseline of 17.8 ± 6.2 to 20.3 ± 5.9 mL/m2 (p 1.9 as specified by Lake Louis criteria) in one or more short axis slices post chemotherapy. There was no new late gadolinium hyperenhancement to suggest focal myocar- dial necrosis/fibrosis in any patient following therapy.

Early and late left ventricular effects of breast cancer chemotherapy: a prospective multi-centre study using advanced cardiac imaging

Background Myocardial dysfunction is a recognized toxicity of anthracycline (A) and herceptin (H) chemotherapy. Whilst there is much current focus on the incidence and magnitude of myocardial dysfunction following the A/H regimen, whether these changes are mediated by reversible or irreversible myocardial injury remains unknown. We sought to determine rates of persistent LV dysfunction at 12 months (as defined by left ventricular ejection fraction (LVEF) decrease by 10% or below lower limits of normal) following A/H and explore the mechanism of myocardial dysfunction using advance cardiac imaging.

Guillain–Barre syndrome in colorectal cancer

Guillain–Barré syndrome has been reported in the setting of different malignancies. To the best of our knowledge, the association of Guillain–Barré syndrome and colorectal cancer has been reported in only two cases. As Guillain–Barré syndrome is potentially life threatening, it should be considered in the differential diagnosis of patients with colorectal cancer with neurological findings. Here we report two cases of Guillain–Barré syndrome in the setting of metastatic colorectal cancer.

Successful renal transplantation after two separate urinary tract malignancies

A patient who was treated for renal cell carcinoma and transitional cell carcinoma, later presented with end stage renal disease. He was managed with hemodialysis and later underwent successful renal transplantation. There was no evidence of tumor recurrence nearly nine years post-renal transplantation.

Contemporary breast cancer chemotherapy leads to persistent late right ventricular myocardial dysfunction: a prospective multi-centre study

Background Previous studies evaluating cardiac effects of chemotherapy have focussed on the left ventricle (LV) and largely been retrospective. Although right ventricle (RV) systolic dysfunction is an adverse prognostic marker in cardiomyopathy states, the RV effects of chemotherapy are not well defined. Methods

PHASE IB/II STUDY OF SECOND LINE THERAPY WITH PANITUMUMAB, IRINOTECAN AND EVEROLIMUS (PIE) IN KRAS WILD TYPE METASTATIC COLORECTAL CANCER

Purpose: Inhibition of mTOR in addition to EGFR may overcome resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC). This phase Ib/II study evaluated the safety and efficacy of the combination of irinotecan, panitumumab, and everolimus. Patients and Methods: Patients with KRAS exon 2 wild-type (WT) mCRC following failure of fluoropyrimidine-based therapy received i.v. irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14-day cycle. The primary endpoint of the phase II study was response rate (RR). Secondary survival outcomes were calculated using the Kaplan–Meier method, and results were analyzed as intention to treat. A preplanned exploratory biomarker analysis was performed. Results: Forty-nine patients were enrolled. Dose level 1 (irinotecan 200 mg/m2, panitumumab 6 mg/kg, and everolimus 5 mg alternate day) was declared the MTD with no dose-limiting toxicities in six patients. Forty patients were treated at dose level 1: median age, 60 years (37–76); 65% male; 45% and 52.5%, respectively, with Eastern Cooperative Oncology Group values of 0/1. Median dose intensity was 85%. Grade 3 toxicities were diarrhea (23%), mucositis (18%), rash (13%), fatigue (8%), dehydration (5%), neutropenia (20%), febrile neutropenia (8%), hypomagnesemia (20%), and hypokalemia (8%). Grade 4 toxicities were hypomagnesemia (5%) and neutropenia (3%). RR was 48%, and stable disease was 43%. Median progression-free survival (PFS) was 5.6 months, and median overall survival (OS) was 10.8 months. Twenty-five patients were RAS/RAF WT and had an RR of 60%, median PFS of 6.4 months, and OS of 11.8 months. Conclusions: The toxicity of the panitumumab, irinotecan, and everolimus regimen is as expected and manageable. The RR of 60% in all RAS/RAF WT supports further study of this combination. Clin Cancer Res; 24(16); 3838–44. ©2018 AACR.

Video-assisted thoracoscopy in the management of intrapleural extravasation of cytotoxic chemotherapy

The extravasation of cytotoxic agents into subcutaneous tissue is a serious complication of chemotherapy. Unfortunately, if such extravasation occurs into the pleural space, limited data is available to guide appropriate management. We present the first report in the literature of video‐assisted thoracoscopy combined with a topoisomerase II inhibitor and iron chelator, dexrazoxane, in the successful management of this complication.

Breast cancer screening—opportunistic use of registry and linked screening data for local evaluation

RATIONALE Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. AIMS AND OBJECTIVES To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. METHODS Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. RESULTS Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. CONCLUSIONS Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected.