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.

A Retrospective Dosimetric Study of Radiotherapy Patients with Left-Sided Breast Cancer; Patient Selection Criteria for Deep Inspiration Breath Hold Technique.

BACKGROUND: Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans. METHODS: Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others). RESULTS: Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient's TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R²). CONCLUSION: The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.

Pharmacovigilance in a rare disease: example of the VIGIAPATH program in pulmonary arterial hypertension.

Spontaneous reporting is the primary method used in pharmacovigilance (PV) to detect drug safety signal. Specific criteria used in pharmacovigilance to prove accountability of a drug are rarely present in rare disease. The low number of alerts also makes it challenging. The aim of this commentary is to raise awareness among pharmacists on issues and opportunities for pharmacovigilance in rare diseases, taking pulmonary arterial hypertension (PAH) as example, from which a subset of cases are drug-induced. It is demonstrated how a dedicated program named VIGIAPATH created to reinforce pharmacovigilance of drug-induced pulmonary arterial hypertension at a national level, led to increase self-reporting and confirm safety signals. Thanks to a specific program such as VIGIAPATH, pharmacists can play an important role in communication with clinicians, patients and regulatory agencies, facilitating the detection of potential safety signals at an early stage in rare disease.

Pulmonary hypertension associated with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a frequent autosomal dominant genetic disorder with a prevalence of 1 in 3000. Pulmonary hypertension (PH) associated with NF1 (PH-NF1) is a rare but severe complication of NF1 and is classified as Group 5 PH, defined as "PH with unclear and/or multifactorial mechanisms". A literature review in PubMed on the association between NF1 and PH identified 18 articles describing 31 cases. PH-NF1 was characterised by a female predominance, an advanced age at diagnosis, an association with parenchymal lung disease in two out of three cases and poor long-term prognosis. NF1 is generally associated with interstitial lung disease but some cases of severe PH without parenchymal lung disease suggest that there could be a specific pulmonary vascular disease. There is no data available on the efficacy of specific pulmonary arterial hypertension treatment in PH-NF1. Therefore, these patients should be evaluated in expert PH centres and referred for lung transplantation at an early stage. As these patients have an increased risk of malignancy, careful assessment of the post-transplant malignancy risk prior to listing for transplantation is necessary. Clinical trials are needed to evaluate promising treatments targeting the RAS-downstream signalling pathways.

Impact of High-Priority Allocation on Lung and Heart-Lung Transplantation for Pulmonary Hypertension.

BACKGROUND: Since 2006 and 2007, patients in France with severe pulmonary hypertension (PH) who are at imminent risk of death, despite optimal treatment in the intensive care unit, are placed on a high-priority list (HPL) for heart-lung transplantation (HLT) or double-lung transplantation (DLT). We assessed the effect of this approach on the waiting list and outcomes after transplantation. METHODS: We conducted a single-center, retrospective, before-and-after study of consecutive patients with severe group 1, 1', or 4 PH listed for DLT or HLT between 2000 and 2013 (ie, 6 years before and 6 years after HPL implementation). RESULTS: We included 234 patients. HPL implementation resulted in a significant decrease of the cumulative incidence of death on the waiting list at 1 and 2 years (p < 0.0001). The cumulative incidence of transplantation increased significantly from 48% to 76% after 2 years (p < 0.0001). Overall survival after transplantation was not significantly different between the pre-HPL and post-HPL era. In the HPL period, patients on the regular list who received a transplant had a nonsignificant trend toward improved overall survival compared with those on the HPL who received a transplant (at 1, 2, 3, and 5 years: 85%, 77%, 72%, and 72% vs 67%, 61%, 58%, and 50%; p = 0.053). Finally, survival after listing improved significantly after HPL implementation (at 1, 2, 3, and 5 years: 69%, 62%, 58%, and 54% vs 54%, 45%, 34%, and 26% before the HPL; p < 0.001). CONCLUSIONS: HPL implementation was followed by higher survival of PH patients after registration on the DLT or HLT waiting list and by a higher cumulative incidence of transplantation among waiting-list patients.

Pulmonary hypertension in patients with neurofibromatosis type I.

Neurofibromatosis type I (NF1) is a rare genetic disease caused by mutations in the NF1 gene, which codes for tumor suppressor neurofibromin. NF1 is transmitted as an autosomal dominant and fully penetrant trait with no sex predominance. Precapillary pulmonary hypertension (PH) is a severe complication of NF1, initially described in patients with advanced parenchymal lung disease, which may complicate the course of NF1. We conducted this study to describe clinical, functional, radiologic, and hemodynamic characteristics and outcome of patients with NF1-associated PH. We identified 8 new cases of NF1-associated PH in patients carrying a NF1 gene mutation. No bone morphogenic protein receptor 2 (BMPR2) point mutation or large size rearrangements were identified. Seven female patients and 1 male patient were reported, suggesting a possible female predominance. PH occurred late in the course of the disease (median age, 62 yr; range, 53-68 yr). Dyspnea and signs of right heart failure were the major symptoms leading to the diagnosis of PH. At diagnosis, patients had severe hemodynamic impairment with low cardiac index (median, 2.3 L/min per m2; range, 1.9-4.7) and elevated indexed pulmonary vascular resistance (median, 15.1 mm Hg/L/min per m2; range, 4.5-25.9). All patients were in New York Heart Association functional class III with severe exercise limitation (median 6-min walk distance, 180 m; range, 60-375 m). Most patients had associated parenchymal lung disease, but some had no or mild lung involvement with disproportionate pulmonary vascular disease. Overall, the impact of PH therapy was limited and outcomes were poor. In conclusion, PH represents a rare but severe complication of NF1, characterized by female predominance, late onset in the course of NF1, and severe functional and hemodynamic impairment. Because of poor outcome and limited impact of specific PH therapy, eligible patients require early referral for lung transplantation. Further studies are needed to better understand the pathophysiology and the role, if any, of neurofibromin in NF1-associated PH.

Clinical impact of, and prognostic stratification by, F-18 FDG PET/CT in head and neck mucosal squamous cell carcinoma.

BACKGROUND: The aim of this study was to determine prospectively the incremental value of positron emission tomography/computed tomography (PET/CT) over conventional assessment (clinical examination and CT/MRI imaging). METHODS: All patients undergoing (18)F-fluorodeoxyglucose (FDG)-PET/CT for primary head and neck mucosal squamous cell carcinoma between January 2002 and December 2003 (inclusive) were included in this study provided they had undergone contemporaneous conventional assessment of the head and neck region and had 12 months minimum follow-up. RESULTS: Seventy-six patients underwent 100 PET/CT scans. The majority of patients (74%) were treated with definitive (chemo)radiotherapy. Median follow-up time was 28 months. PET/CT led to a TNM classification alteration in 34% (12/35), a change in radiotherapy planning technique and/or dose in 29% (10/35), and altered treatment response assessment in 43% (13/30). A complete metabolic response was predictive of overall survival (p = .037). CONCLUSION: Our results support incorporation of PET/CT into the management paradigm of head and neck mucosal squamous cell carcinoma.