Disseminated intravascular coagulation complicating diagnosis of ROS1-mutant non-small cell lung cancer: A case report and literature review.

Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6-6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene-addicted lung cancers, especially those containing ROS proto-oncogene 1 (ROS1) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1-mutant non-small-cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of life-threatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation.

Patterns of follow-up care after curative radiotherapy ± chemotherapy for stage I-III non-small cell lung cancer.

OBJECTIVES: To describe patterns of follow-up care for non-small cell lung cancer patients treated with curative radiotherapy and to evaluate the role of routine imaging. MATERIALS AND METHODS: We retrospectively analyzed follow-up care of patients with stage I-III non-small cell lung cancer treated with curative radiotherapy (minimum dose of 50 Gy) between 2007 and 2011 at three Sydney institutions. Patient demographics, tumor characteristics and treatment factors were collected from oncology and hospital records. Follow-up visits were recorded until an event (recurrence or new primary) was diagnosed or censor date was reached (December 31, 2016). Univariate and multivariate analyses were performed to identify factors associated with subsequent curative treatment and survival. RESULTS: Two-hundred and eighty-three patients were identified with a median age of 72 (36-91) years. Median number of follow-up visits was 6, and median time to first event was 10.8 months. Follow-up visits were by routine appointment in 74%, and symptomatic presentation in 26%. Variation in follow-up was seen across the three institutions in terms of imaging conducted and specialist seen. Recurrences were diagnosed in 175 patients of whom 85 were symptomatic and 90 diagnosed on routine imaging. New primaries were diagnosed in 23 patients, 18 with symptoms and 5 on routine imaging. Subsequent treatment was curative in 17 (10%) patients with recurrent disease and 18 (78%) with new primaries. On multivariable analysis, symptomatic diagnosis (P = 0.006) was associated with subsequent curative treatment but not with overall survival (P > 0.05). CONCLUSION: The follow-up of patients showed considerable variation between institutions. Routine imaging was not associated with subsequent curative treatment of events or improved overall survival.

Radiotherapy patterns of care for stage I and II non-small cell lung cancer in Sydney, Australia.

INTRODUCTION: Curative radiotherapy is guideline treatment for inoperable patients of good performance status with Stage I & II Non-Small Cell Lung Cancer (NSCLC). The aim of this study was to evaluate radiotherapy patterns of care in these patients, the reasons for palliative treatment and the proportion of patients suitable for curative stereotactic ablative body radiotherapy (SABR). METHODS: Electronic oncology databases at three institutions were queried to retrieve data on patients with inoperable Stage I & II NSCLC seen in radiation oncology clinics between 1/1/2008 and 31/12/2014. Suitability for SABR was defined as peripheral tumours less than 5 cm in size. Factors associated with curative treatment were determined using univariate and multivariate analyses. RESULTS: Three-hundred-and-twelve patients were identified of whom 178 (57%) received curative radiotherapy, 58 (19%) palliative radiotherapy and 76 (24%) no radiotherapy. The main reason for receiving palliative rather than curative treatment was COPD or poor pulmonary function (26%). Method of diagnosis (P = 0.031), Simplified Comorbidity Score (P = 0.003), ECOG performance status (P = 0.016), FEV1% (P = 0.040), treating institution (P < 0.0001) and time period (P = 0.016) were associated with curative radiotherapy on multivariate analysis. In patients with T1-2N0M0 NSCLC, 19 (31%) who did not receive treatment and 7 (21%) who underwent palliative radiotherapy were technically and clinically suitable for SABR. CONCLUSION: Only 57% of patients with Stage I-II NSCLC were treated with curative radiotherapy. Patient factors were the predominant reason for palliative treatment, however, treating institution also played a role. A considerable proportion of patients who underwent palliative or no radiotherapy were suitable for SABR treatment.

Iodine-125 prostate seed brachytherapy in renal transplant recipients: an analysis of oncological outcomes and toxicity profile.

PURPOSE: Prostate cancer is among the most common non-cutaneous neoplasms affecting renal transplant recipients (RTRs). Available treatments including radical prostatectomy and external beam radiotherapy carry a risk of damage to the transplanted kidney, ureters, or bladder. We assessed the safety and efficacy of Iodine-125 ((125)I) prostate seed brachytherapy as an alternative to surgery and radiotherapy in these individuals. MATERIAL AND METHODS: We retrospectively reviewed our brachytherapy database to identify patients with a prior history of renal transplantation, who had undergone seed implantation for localized prostate cancer. Long term PSA control and treatment related toxicity, including graft dysfunction, urinary, rectal, and sexual complications, were assessed and compared with published outcomes for surgery and external beam radiotherapy. RESULTS: Of 1054 patients treated with permanent seed implantation from 2002-2012, we identified four who had a prior history of renal transplantation. Mean time from renal transplantation to prostate cancer diagnosis was 13 years. Mean follow-up after seed implantation was 44 months (range 12-60 months). All four patients remain free of PSA progression. No peri-operative complications were experienced following seed implantation, and all four patients continued to have normal graft function. Long term urinary and rectal function scores were comparable to reported outcomes for seed brachytherapy in the non-transplant population. CONCLUSIONS: (125)I prostate seed brachytherapy is associated with high rates of biochemical control and minimal toxicity to the renal graft in RTRs. This treatment should be considered as an alternative to surgery in managing RTRs with localized prostate cancer.

Iodine-125 thin seeds decrease prostate swelling during transperineal interstitial permanent prostate brachytherapy.

INTRODUCTION: Prostate swelling following seed implantation is a well-recognised phenomenon. The purpose of this intervention was to assess whether using thinner seeds reduces post-implant swelling with permanent prostate brachytherapy. METHODS: Eighteen consecutive patients eligible for prostate seed brachytherapy underwent seed implantation using iodine-125 (I-125) thin seeds. Operative time, dosimetry, prostate swelling and toxicity were assessed and compared with standard I-125 stranded seed controls, sourced from the department's brachytherapy database. RESULTS: A learning curve was noted with the thin seeds in terms of greater bending and deviation of needles from their intended path. This translated into significantly longer total operative time (88 vs 103 minutes; P = 0.009, 95% confidence interval (CI) 4.1-24.3) and time per needle insertion (2.6 vs 3.7 minutes; P < 0.001, 95% CI 0.5-1.3) for the thin seeds. Day 30 prostate volumes were significantly smaller in the thin seed group compared with standard seeds (40.9 cc vs 46.8 cc; P = 0.001, 95% CI 1.5-5.6). The ratio of preoperative transrectal ultrasound to day 30 post-implant CT volume was also smaller in the thin seed group (1.2 ± 0.1 for standard seeds vs 1.1 ± 0.1 for thin seeds). Post-implant dosimetric parameters were comparable for both groups. No significant differences were seen in acute urinary morbidity or quality of life between the two groups. CONCLUSIONS: I-125 thin seeds are associated with an initial learning curve, with longer operative time, even for experienced brachytherapists. The significant reduction in day 30 prostate volumes with the thin seeds has useful implications in terms of optimising dose coverage to the prostate in the early period post-implantation, as well as improving the accuracy of post-implant dosimetric assessments.

Prospective study of exercise intervention in prostate cancer patients on androgen deprivation therapy.

INTRODUCTION: Androgen deprivation therapy (ADT) is an important component of modern prostate cancer treatment. Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest, and balancing this with potential morbidity of therapy can be challenging. This study aimed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT. METHODS: Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home) exercise or a support programme for those incapable of exercising (Support). Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion. Patients in the exercise streams were surveyed to determine the programme's impact on physical fitness and well-being. RESULTS: Statistically significant improvements (p < 0.001) were seen in all measured cardiorespiratory fitness and strength variables. Programme attrition rates were low (75/859; 8.7%), the primary reason for withdrawal being discontinuation of hormones (70%). Programme satisfaction was high, with 98% of surveyed patients reporting a positive impact on fitness and 97% planning to continue exercising after programme completion. At 6 months, improved physical and emotional well-being was reported by 93 and 79% of patients, respectively. CONCLUSIONS: A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT.

First report of transperineal polyethylene glycol hydrogel spacer use to curtail rectal radiation dose after permanent iodine-125 prostate brachytherapy.

PURPOSE: To demonstrate the feasibility of transperineal polyethylene glycol (PEG) hydrogel insertion into anterior perirectal fat for reducing rectal radiation dose in patients with suboptimal rectal dosimetry after permanent iodine-125 prostate brachytherapy. METHODS AND MATERIALS: Five patients with suboptimal rectal dosimetry after iodine-125 seed brachytherapy implant underwent a single transperineal injection of PEG hydrogel into the anterior perirectal fat under general anesthetic using transrectal ultrasound guidance. Prostate-rectum separation and rectal radiation dose before and after PEG hydrogel spacer insertion were measured. Toxicity because of spacer insertion was assessed at Days 0-1 and 4-6 weeks using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: All patients experienced a clinically significant reduction in the volume of rectum receiving greater than or equal to the prescription dose (RV100) on the postspacer postimplant dosimetry, compared with the prespacer postimplant dosimetry. Mean prostate-rectum separation that was achieved with the insertion of the spacer was 15.1 mm (±3.4). The mean difference in separation from before to after spacer insertion was 12.5 mm (±4.5). This was associated with a reduction in mean RV100 from 3.04 (±1.2) to 0.06 (±0.1) cc. Toxicities were limited to Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) perineal pain and rectal discomfort (3/5 patients). There were no Grade 2 or greater toxicities reported after insertion of the spacer. CONCLUSIONS: PEG hydrogel is safe and effective at reducing rectal radiation dose in select patients with suboptimal rectal dosimetry after prostate seed brachytherapy.

Metastatic Cutaneous Squamous Cell Carcinoma to the Axilla: A Review of Patient Outcomes and Implications for Future Practice.

BACKGROUND: Nodal metastasis from cutaneous SCC carries a high morbidity and mortality. Limited direct evidence is available as to the impact of radiotherapy on the outcome of patients with metastatic axillary SCC. The purpose of this study was to report on the outcomes of patients with metastatic cutaneous SCC to the axilla treated with radiotherapy. METHODS: A retrospective review of patients treated with radiotherapy between 1993 and 2010 for metastatic cutaneous SCC to the axilla was undertaken at St George Hospital, Sydney. RESULTS: Radiotherapy was administered to 36 patients, 30 with curative intent (4 definitive, 26 adjuvant) and 6 with palliative intent, 27/36 (75%) were male, 22/36 (61%) had a previous diagnosis of cutaneous SCC, and 1/36 (3%) was immunosuppressed. Mean age was 74.6 years. Mean radiotherapy dose (BEDGy10) was 61Gy10 (range 39-85 Gy10), 20/36 (56%) patients experienced recurrence, including 16 local failures and 4 isolated distant failures. Median survival for the curative and palliative groups was 3 years and 1 month, respectively. Relapse free survival (n = 36) at 2 and 5 years was 46% and 35%, respectively (curative 52% and 39%). Only 1 failure achieved complete salvage. CONCLUSION: Despite current best practice (surgery and radiotherapy), the predominant pattern of failure in these patients with metastatic axillary cSCC was locoregional. The difficulty in successfully salvaging patients after locoregional nodal relapse suggests a need for treatment intensification.