Cardiovascular risk factors and pulmonary function in long-term survivors of testicular cancer

Paper 2 of the thesis is not available in Munin due to publisher's restrictions: 2. Haugnes HS, Aass N, Fosså SD, Dahl O, Klepp O, Wist EA, Svartberg J, Wilsgaard T, Bremnes RM.: 'Components of the metabolic syndrome in long-term survivors of testicular cancer.' Annals of Oncology 18:241-248, 2007 (Oxford University Press), available at http://dx.doi.org/10.1093/annonc/mdl372Testikkelkreft er den vanligste kreftformen blant unge menn, og >95 % blir i dag helbredet av sykdommen. Dermed er kunnskap om mulige seneffekter etter behandlingen viktig. Avhandlingen ”Cardiovascular risk factors and pulmonary function in long-term survivors of testicular cancer” ble forsvart for graden ph.d 24. april 2009. Takket være effektiv cytostatikabehandling som ble tatt i bruk på slutten av 70-tallet, er overlevelsen ved metastatisk testikkelkreft blitt betraktelig bedret de siste 30 årene. Standard behandling ved metastatisk testikkelkreft er i dag 3-4 kurer med cisplatin-basert kjemoterapi. Behandlingsmuligheter for pasienter med lokal sykdom er operasjon, stråleterapi eller kun en kjemoterapikur. Siden denne sykdommen primært rammer menn i 20- og 30-årene, og disse forventes å ha en nærmest normal levetid etter behandlingen, er det svært viktig å avklare om behandlingen kan føre til senbivirkninger. Vi har sett spesielt på risikofaktorer for kardiovaskulær sykdom og lungefunksjonen og om disse kan være relatert til noen av behandlingstypene. Avhandlingen er basert på en landsomfattende etterkontroll av norske menn som ble behandlet og kurert for testikkelkreft i perioden 1980-1994. Etterkontrollen ble utført ved fem universitetsklinikker i perioden 1998-2002, og bestod av et omfattende spørreskjema, klinisk undersøkelse ved kreftpoliklinikk inkludert måling av blodtrykk, vekt, høyde, blodprøver og spirometri. Totalt ble 1814 menn invitert til å delta, og av disse var det 1463 (81 %) som deltok. En kontrollgruppe bestående av menn uten tidligere testikkelkreft ble etablert gjennom Tromsøundersøkelsen. Vi fant ut at menn som tidligere var blitt behandlet med cisplatinbasert cytostatika, særlig i høye doser, hadde høyere forekomst av hypertensjon, fedme og metabolsk syndrom, både sammenlignet med menn som kun var behandlet med kirurgi og sammenlignet med kontroller. Menn behandlet med høye doser cisplatinbasert cytostatika og kombinasjonen cytostatika/lungekirurgi hadde redusert lungefunksjon sammenlignet med menn behandlet med kirurgi alene. Mennene som var blitt behandlet med cytostatika hadde også lavere nivåer av testosteron. Behandling med stråleterapi påvirket ikke kardiovaskulære risikofaktorer eller lungefunksjonen

The Longitudinal Course of Prospectively Recorded Patient-reported Outcomes in Prostate Cancer Patients Treated with Surgery and Salvage Radiotherapy

Background - Patient-reported outcome measures (PROMs) after prostate cancer (PC) treatment, including both radical prostatectomy (RP) and salvage radiation therapy (SRT), are under-reported. Objective - To investigate PROMs longitudinally from before SRT until 18 mo after SRT for men treated with contemporary treatment modalities. Design, setting, and participants - This prospective, longitudinal cohort study included 120 men (whole cohort) treated with SRT administered with volumetric modulated arc radiotherapy from 2016 to 2021 at the University Hospital of North Norway. The whole cohort was followed from before SRT until 18 mo after SRT. A subcohort of 48 men was followed from before RP until 18 mo after SRT. Outcome measurements and statistical analysis - PROMs were collected with the Expanded Prostate Cancer Index-26 (EPIC-26), covering symptoms of urinary incontinence, urinary irritative, bowel, sexual, and hormonal domains. The domain scores were inquired before RP, 3 mo after RP, before SRT, at SRT termination, and 3 and 18 mo after SRT. We used linear mixed models with repeated measurements design to assess changes in PROMs throughout the treatment period. Results and limitations - The median age before SRT was 63 yr. For the whole cohort, all five domains worsened at 3 and 18 mo after SRT compared with those before SRT. The estimated mean changes from before SRT to 18 mo after SRT are as follows: urinary incontinence –13.1, urinary irritative function –10.4, bowel –16.8, sexual function –9.1, and hormonal function –20.2 (at clinically important levels for all domains but sexual). For the subcohort, the mean urinary incontinence, bowel, sexual, and hormonal functions were significantly worsened 3 and 18 mo after SRT compared with those before RP at clinically important levels. Conclusions - Men treated for PC report particular increased severity of urinary, bowel, sexual, and hormonal symptoms after SRT compared with baseline status

Association of physical activity with overall mortality among long-term testicular cancer survivors: A longitudinal study

Physical activity (PA) has been associated with reduced mortality among cancer survivors, but no study has focused on testicular cancer survivors (TCSs). We aimed to investigate the association of PA measured twice during survivorship with overall mortality in TCSs. TCSs treated during 1980 to 1994 participated in a nationwide longitudinal survey between 1998 to 2002 (S1: n = 1392) and 2007 to 2009 (S2: n = 1011). PA was self-reported by asking for the average hours per week of leisure-time PA in the past year. Responses were converted into metabolic equivalent task hours/week (MET-h/wk) and participants were categorized into: Inactives (0 MET-h/wk), Low-Actives (2-6 MET-h/wk), Actives (10-18 MET-h/wk) and High-Actives (20-48 MET-h/wk). Mortality from S1 and S2, respectively, was analyzed using the Kaplan-Meier estimator and Cox proportional hazards models until the End of Study (December 31, 2020). Mean age at S1 was 45 years (SD 10.2). Nineteen percent (n = 268) of TCSs died between S1 and EoS, with 138 dying after S2. Compared to Inactives at S1, the mortality risk among Actives was 51% lower (HR 0.49, 95% CI: 0.29-0.84) with no further mortality reduction among High-Actives. At S2, the mortality risk was at least 60% lower among the Actives, High-Actives and even the Low-Actives compared to the Inactives. Persistent Actives (≥10 MET-h/wk at S1 and S2) had a 51% lower mortality risk compared to Persistent Inactives (<10 MET-h/wk at S1 and S2; HR 0.49, 95% CI: 0.30-0.82). During long-term survivorship after TC treatment, regular and maintained PA were associated with an overall mortality risk reduction of at least 50%

Patient-reported outcomes after curative treatment for prostate cancer with prostatectomy, primary radiotherapy or salvage radiotherapy

Trials reporting adverse health outcomes (AHOs) in terms of patient-reported outcome measures (PROMs) after contemporary curative treatment of prostate cancer (PC) are hampered by study heterogeneity and lack of new treatment techniques. Particularly, the evidence regarding toxicities after radiotherapy (RT) with the volumetric arc therapy (VMAT) technique is limited, and comparisons between men treated with surgery, primary radiotherapy (PRT) and salvage radiotherapy (SRT) are lacking. The aim of the study was to evaluate change in PROMs 3 months after treatment with robotic-assisted laparoscopic prostatectomy (RALP), PRT and SRT administered with VMAT

Thromboembolic events after high-intensity training duringcisplatin-based chemotherapy for testicular cancer: Casereports and review of the literature

The randomized “Testicular cancer and Aerobic and Strength Training trial” (TAST‐trial) aimed to evaluate the effect of high‐intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin‐based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session. The exercise intervention included two weekly HIIT sessions, each with 2 to 4 intervals of 2 to 4 minutes at 85% to 95% of peak heart rate. The study was prematurely discontinued after inclusion of 19 of the planned 94 patients, with nine patients randomized to the intervention arm and 10 to the control arm. Three patients in the intervention arm developed TE complications; two with pulmonary embolism and one with myocardial infarction. All three patients had clinical stage IIA TC. No TE complications were observed among patients in the control arm. Our observations indicate that high‐intensity aerobic training during CBCT might increase the risk of TE events in TC patients, leading to premature closure of the TAST‐trial

Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry

Purpose Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. Patients and Methods We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. Results Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. Conclusion FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone

Most common health problems in general practice among adolescents, and young adults’ survivors of lymphoma: a register-based cohort study in Norway

Background - The aim was to investigate the distribution of health problems in general practice (GP) among adolescent and young adult (AYA) survivors of lymphoma and to compare problem rates with the general population. Methods - All GP consultations between 2006 and 2020 were identified from the national GP claims register. Diseases and complaints presented 3–10 years after the cancer diagnosis were identified using the International Classification of Primary Care codes (ICPC-2) and compared by applying logistic regression models, presented with odds ratio (OR) and 95%CI. Results - A total of 2,500,557 AYAs, of whom 1105 were diagnosed with lymphoma, and over 50 million GP consultations were included. The most common causes of consultation among AYA survivors of lymphoma were related to Hodgkin’s disease (13%), pregnancy (11%), respiratory diseases (9%), psychological problems (8%), musculoskeletal system (6%) and fatigue (4%). Almost all these problems were significantly higher among AYA lymphoma survivors compared to the general population (OR ranging from 1.1 to 1.5). Conclusion - Compared to the general population, young lymphoma survivors have increased contact with the GP for a considerable number of health problems for up to 10 years post-diagnosis. This emphasizes the importance of robust follow-up and a good flow of information between hospital and primary care