Outcomes Following Treatment with FOLFOX for Patients with Resectable or Potentially Resectable Metastatic Colorectal Cancer: A Population-based Cohort Study.

AIMS: To evaluate the safety and effectiveness of oxaliplatin-based combination chemotherapy for patients with metastatic colorectal cancer (mCRC) to extrahepatic sites. MATERIALS AND METHODS: We conducted a population-based retrospective study examining the safety and effectiveness of perioperative oxaliplatin for resectable or potentially resectable colorectal metastases in Ontario, Canada. Outcomes were also compared with patients with liver-only metastases. Patients received oxaliplatin for mCRC between 1 January 2013 and 30 June 2020. RESULTS: In total, 192 patients had extrahepatic metastases. Seventy per cent had R0 metastasectomy. The 3-year disease-free survival and overall survival were 62% and 79%, respectively; <4% of patients died within 60 days of metastasectomy and 74-90% of patients received treatment according to recommendations from a multidisciplinary setting. Compared with liver-only controls (n = 1306), patients had mCRC to the lung only (n = 115), lung and liver (n = 55) and liver with non-pulmonary site (n = 22). Extrahepatic metastases were more likely to be found for patients whose primary colorectal resection had positive margins (14% versus 7%, P = 0.005) and primary tumours located in the rectum [odds ratio 4.01 (2.31-6.97)]. After adjustment, there was no difference in overall survival between liver-only controls and patients with lung-only [hazard ratio 0.82 (0.59-1.15)] or liver and lung metastases [hazard ratio 1.26 (0.85-1.87)] (P = 0.24). In total, 79/115 (69%) of patients with lung-only metastases had a metastasectomy compared with 645/1306 (49%) and 15/55 (27%) of patients with liver-only and liver and lung metastases, respectively. Hospital visits were similar between patients with liver-only and extrahepatic metastases. CONCLUSION: Oxaliplatin-based chemotherapy for patients with resectable or potentially resectable mCRC with extrahepatic metastases was safe and resulted in similar outcomes in appropriately selected patients when compared with patients with liver-only metastases.

Association between waiting time for radiotherapy after surgery for early-stage breast cancer and survival outcomes in Ontario: a population-based outcomes study.

Background: After surgery for early-stage breast cancer (bca), adjuvant radiotherapy (rt) decreases the risk of locoregional recurrence and death from bca. It is unclear whether delays to the initiation of adjuvant rt are associated with inferior survival outcomes. Methods: This population-based retrospective cohort study included a random sample of 25% of all women with stage i or ii bca treated with adjuvant rt in Ontario between 1 September 2001 and 31 August 2002, when, because of capacity issues, wait times for radiation were abnormally long. Pathology reports were manually abstracted and deterministically linked to population-level administrative databases to obtain information about recurrence and survival outcomes. Cox proportional hazards modelling was used to evaluate the association between waiting time and survival outcomes. A composite survival outcome was used to ensure that all possible measurable harms of delay would be captured. The composite outcome, event-free survival, included locoregional recurrence, development of metastatic disease, and bca-specific mortality. Results: We identified 1028 women with stage i or ii bca who were treated with breast-conserving surgery and adjuvant rt. For the 599 women who were treated with adjuvant radiation without intervening chemotherapy, a waiting time of 12 weeks or more from surgery to the start of radiation appeared to be associated with worse event-free survival after a median follow-up of 7.2 years (hazard ratio for the composite outcome: 1.44; 95% confidence interval: 0.98 to 2.11; p = 0.07). For the 429 women who received intervening adjuvant chemotherapy, a waiting time of 6 weeks or more from completion of chemotherapy to start of radiation was associated with worse event-free survival after a median follow-up of 7.4 years (hazard ratio: 1.50; 95% confidence interval: 1.00 to 2.22; p = 0.047). Conclusions: Delay to the initiation of adjuvant rt after breast-conserving surgery is associated with inferior bca survival outcomes. The good prognosis for patients with early-stage bca limits the statistical power to detect an effect of delay to rt. Given that there is no plausible advantage to delay, we agree with Mackillop that time to initiation of rt should be kept "as short as reasonably achievable."

A population-based study of pulmonary monitoring and toxicity for patients with testicular cancer treated with bleomycin.

Background: Bleomycin is commonly used to treat advanced testicular cancer and can be associated with severe pulmonary toxicity. The primary objective of the present study was to describe the use of pulmonary function tests (pfts) and chest imaging before, during, and after treatment with bleomycin. Methods: To identify all incident cases of testicular cancer treated with bleomycin-based chemotherapy in the Canadian province of Ontario during 2005-2010, the Ontario Cancer Registry was linked with chemotherapy treatment records. Health administrative databases were used to describe use of pfts, chest imaging, and physician visits for respiratory complaints. Results: Of 394 patients treated with orchiectomy and chemotherapy who received at least 1 dose of bleomycin, 93% had complete chemotherapy records available. In the 4 weeks before, during, and within 2 years after finishing bleomycin-based chemotherapy, pfts were performed in 17%, 17%, and 29% of patients respectively. Chest imaging was performed in 68%, 62%, and 98% of patients in the same time periods. In the 2 years after bleomycin-based chemotherapy, 23% of treated patients had a physician visit for respiratory symptoms. That rate was substantially higher for men with greater exposure to bleomycin: 40% (24 of 60) for 10-12 doses bleomycin compared with 21% (53 of 250) for 7-9 doses and with 14% (8 of 58) for 1-6 doses (p = 0.002). Conclusions: Quality improvement initiatives are needed to increase baseline rates of chest imaging within 4 weeks of starting chemotherapy for testicular cancer; to understand why such a high proportion of men have chest imaging during bleomycin-based chemotherapy; and to mitigate the excess pulmonary toxicity seen with increasing exposure to bleomycin.

Venous Thromboembolism During Chemotherapy for Testicular Cancer: A Population-Based Study.

AIMS: Venous thromboembolism (VTE) is a potential complication among germ cell tumour patients. We evaluated the incidence rate, timing and factors associated with VTE among patients with germ cell cancer in routine practice. MATERIALS AND METHODS: The Ontario Cancer Registry was linked to electronic records of treatment to identify all cases of testicular cancer treated in Ontario during 2000-2010. Administrative databases were used to identify VTE in the 3 months before and 5 years after orchiectomy. We explored patient-, disease- and treatment-related factors associated with VTE among all patients as well as those with detailed chemotherapy records available. RESULTS: During 2000-2010, 2650 patients underwent orchiectomy for testicular cancer; among this cohort, 920 (33%) received chemotherapy. The VTE rate was 8% (69/920) among patients treated with chemotherapy and 0.6% (11/1730) among those without chemotherapy. Among the patients treated with chemotherapy who had VTE, 13% (9/69) occurred in the month before starting chemotherapy, 62% (42/69) in the first 3 months after starting and 25% thereafter. For patients who received three and four cycles, VTE rates were 8% (21/258) and 16% (19/121), respectively. In adjusted analyses, the only factor independently associated with VTE was increasing number of cycles (odds ratio 3.91 for four cycles, odds ratio 1.63 for three cycles (P = 0.022) compared with one to two cycles). CONCLUSION: This population-based study confirms findings from institutional case series regarding the high rate of VTE among patients with germ cell tumours treated with chemotherapy. Future studies should evaluate the extent to which VTE prophylactic strategies might mitigate this risk.

Neurotoxicity Among Survivors of Testicular Cancer: A Population-based Study.

AIMS: Neurotoxicity may affect the quality of life of survivors of testicular cancer. Understanding the burden of neurotoxicity is important to guide survivorship care. A population-based study was undertaken to describe the proportion of patients in the 'real world' with neurotoxicity. MATERIALS AND METHODS: A population-based, retrospective, cohort study of patients with advanced testicular cancer treated in the province of Ontario. The Ontario Cancer Registry was linked to electronic treatment records to identify all incident cases of testicular cancer during 2000-2010. Administrative databases were used to describe health system visits for symptoms potentially related to neurotoxicity. Health system visit rates were explored by number of chemotherapy cycles among patients treated during 2005-2010 for whom complete chemotherapy details were available. RESULTS: During 2000-2010, 2650 patients underwent an orchiectomy for testicular cancer; 920 (33%) also received chemotherapy. The proportion of patients with health system visits for neurotoxicity in the 2 years before surgery compared with the 2 years after surgery remained stable among patients treated with orchiectomy alone (18% [303/1730] versus 18% [316/1730], P = 0.523); however, there was a substantial increase among patients treated with chemotherapy (16% [151/920] versus 25% [231/920], P < 0.001). Among patients treated with chemotherapy in 2005-2010 for whom complete details were available regarding number of treatment cycles there was a dose-response effect. The increase in health system visits for neurotoxicity from 2 years before compared with 2 years after orchiectomy was greater among patients treated with four cycles of chemotherapy (17% [21/121] versus 37% [45/121]) and three cycles of chemotherapy (17% [45/258] versus 28% [72/258]) compared with those treated with one to two cycles of chemotherapy (<13% [<6/45] versus 20% [9/45], P = 0.013). CONCLUSIONS: This population-based study suggests that symptoms of neurotoxicity are common among survivors of testicular cancer and that this seems to be driven by increasing exposure to chemotherapy. Clinicians should carefully evaluate patients for neurotoxicity during the survivorship phase of treatment.

Therapeutic defibrination and heparin therapy in the prevention and resolution of experimental venous thrombosis.

The application of phenol to the femoral veins of anesthetized dogs resulted in an occluding thrombus in 24 of 25 veins at 1 week. Serial venography and eventual histology showed that these veins remained occluded over a 5-week observation period, the thrombi undergoing organization. Therapeutic defibrination was achieved with administration of an enzyme from venom of the pit viper (Arvin). Arvin, administered for 1 week immediately following phenol application and before thrombus formation had occurred, prevented thrombosis in all 10 such veins, and serial venography for a further 4 weeks showed that the veins remained patent. Administration of Arvin was begun 24 hours postoperatively, when venography had demonstrated an occluding thrombus and failed to clear any of 11 veins after 3 weeks of treatment. Intravenous administration of heparin, 10,000 units, at 6, 6, and 12-hour intervals in a 24-hour period, was begun immediately after phenol application and continued for 1 week; 10 of 12 veins were blocked at 1 week. Following the same dose of heparin every 6 hours four of eight veins were blocked at 1 week. The results indicate that when the vascular endothelium is damaged, therapeutic defibrination is more effective than heparin therapy in preventing venous thrombosis. Arvin therapy has no significant thrombolytic effect even if the thrombus is less than 24 hours old.

Continuous imaging of regional myocardial blood flow in dogs using krypton-81m.

The unique physical properties of the freely diffusible gas krypton-81 m allowed continuous imaging of regional myocardial blood flow in dogs when infused into the aortic root. Regional changes in myocardial perfusion related to transient coronary artery occlusion were demonstrated both as high resolution gamma camera images and as a quantitative strip chart record.

The functional defect in amyloid heart disease. The "stiff heart" syndrome.

Left ventricular performance was studied in three patients with heart failure due to amyloid deposits. The diagnosis of amyloidosis was proved by cardiac biopsy in two patients and by rectal biopsy in the third. One patient had myelomatosis, but the other two had no other identifiable disease. The investigative technique allowed simultaneous measurements of pressure and volume in the left ventricle. The functional defect with slow cardiac filling at high pressure and greatly reduced left ventricular contraction differed from that of constrictive pericarditis and other heart muscle disease. These features of a "stiff heart" are probably unique to amyloidosis and should make possible positive recognition of the condition on the basis of echocardiographic, angiographic and hemodynamic findings.

Comparison of the ST/heart rate slope with the modified Bruce exercise test in the detection of coronary artery disease.

The rate of depression of the ST segment with increasing heart rate (HR) during exercise has been claimed to predict the extent of coronary artery disease (CAD). To determine whether the maximal ST/HR slope is better than the Bruce treadmill exercise test for predicting the presence of CAD, the maximal ST segment/HR slope was calculated in 81 patients and compared with the results of a standard 12-lead exercise test. In 21 patients (26%), the ST/HR slope could not be calculated. In 60 patients with ST/HR slope values, the extent of CAD was predicted in 24 patients (40%). The sensitivity and specificity of the ST/HR slope in predicting the presence of CAD in the 60 patients with slope values were 91% and 27%, respectively. The sensitivity and specificity of the modified Bruce treadmill exercise test in the 81 patients were 81% and 64%, respectively. Thus, the use of the ST/HR slope does not provide additional information that cannot be obtained using the standard Bruce exercise test.

Assessment of organ radiation doses and associated risk for digital bifemoral arteriography.

An assessment has been made of the absorbed dose associated with femoral arteriography using a digital imaging system. A bilateral femoral arteriogram was performed on 17 patients, using a filmless 1024 matrix digital image acquisition system with a discrete stepping tube-stand and 40 cm image intensifier. A standardized protocol of manual patient/tube-stand positioning under fluoroscopic control and automatic stepping digital acquisition was followed. Skin entry doses were measured with a dose-area product meter for each stage of the procedure, and the total gonad dose was assessed with thermoluminescent dosimeters (TLDs). Published Monte Carlo simulations were supplemented with further calculations to evaluate organ doses from the dose-area products measured. Comparison with the TLD measurements indicated that this technique over-estimated organ doses by about 30%. A mean effective dose of 3.1 +/- 1.8 mSv was calculated for the procedure, with the greatest dose burden being imposed by fluoroscopy during catheter manipulation. The related radiation detriment is 0.018%, which is insignificant when compared with the overall mortality from peripheral vascular disease.