Third-line Life-prolonging Drug Treatment in a Real-world Metastatic Castration-resistant Prostate Cancer Population: Results from the Dutch Castration-resistant Prostate Cancer Registry.

BACKGROUND: Evidence concerning third-line life-prolonging drugs (LPDs) in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients is incomplete. OBJECTIVE: To evaluate third-line LPD outcomes in a real-world cohort of mCRPC patients, identify variables associated with overall survival (OS), and establish a prognostic model. DESIGN, SETTING, AND PARTICIPANTS: Patients with mCRPC who were progressive on second-line LPD before July 1, 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed until December 31, 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association of potential risk factors with OS was tested by Cox proportional hazard models after multiple imputation of missing baseline characteristics. A predictive score was computed from the regression coefficient and used to classify patients into risk groups. RESULTS AND LIMITATIONS: Of 1011 mCRPC patients progressive on second-line LPD, 602 (60%) received third-line LPD. Patients receiving third-line LPD had a more favorable prognostic profile at baseline and longer median OS than patients with best supportive care (10.4 vs 2.4 mo, p < 0.001). Eastern Cooperative Oncology Group performance status 1 and ≥2 (hazard ratio [HR] 1.51, p < 0.007 and HR 3.08, p < 0.001, respectively), opioid use (HR 1.55, p = 0.019), visceral metastases (HR 2.09, p < 0.001), hemoglobin <7 mmol/l (HR 1.44, p < 0.002), prostate-specific antigen ≥130 µg/l (HR 1.48, p = 0.001), alkaline phosphatase ≥170 U/l (HR 1.52, p < 0.001), and lactate dehydrogenase ≥250 U/l (HR 1.44; p = 0.015) were associated with shorter survival. Harrell's C-index was 0.74. The median OS values for low-, low-intermediate-, high-intermediate-, and high-risk groups were 14, 7.7, 4.7, and 1.8 mo, respectively. Limitations include the retrospective design. CONCLUSIONS: We developed a prognostic model and identified a subgroup of patients in whom third-line LPD treatment has no meaningful benefit. Our results need to be confirmed by prospective clinical trials. PATIENT SUMMARY: We reported outcomes from third-line life-prolonging drugs in metastatic prostate cancer patients and developed a prognostic model that could be used to guide treatment decisions.

Brain abnormalities on MRI in non-functioning pituitary adenoma patients treated with or without postoperative radiotherapy.

BACKGROUND AND PURPOSE: To assess and compare brain abnormalities on Magnetic Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients treated with or without postoperative radiotherapy (RT). MATERIAL AND METHODS: In 86 NFA patients, treated between 1987 and 2008 at the University Medical Center Groningen, white-matter lesions (WMLs), cerebral atrophy, brain infarctions and abnormalities of the temporal lobes and hippocampi were assessed on pre- and post-treatment MRI scans in patients treated with (n=47) or without RT. RESULTS: The median MRI follow-up time for RT patients was 10 (range 1-22) years and 5 (range 1-21) years in patients treated without RT. In RT patients the cumulative incidence of WMLs was significantly lower compared to patients treated without RT (log-rank test RR 0.49, 95% CI 0.25-0.97, p=.042). The cumulative incidences of cerebral atrophy, brain infarctions, abnormalities of the temporal lobes and hippocampi, and the severity of WMLs and cerebral atrophy ratings were not significantly different between the two treatment groups. CONCLUSIONS: Brain abnormalities on MRI are not observed more frequently in NFA patients treated with RT compared to patients treated with surgery-alone. Furthermore, RT was not associated with an increased severity of WMLs and cerebral atrophy ratings in this cohort of NFA patients.

Incidence, causative mechanisms, and anatomic localization of stroke in pituitary adenoma patients treated with postoperative radiation therapy versus surgery alone.

PURPOSE: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. METHODS AND MATERIALS: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed after surgery alone. Risk factors for stroke incidence were studied by log-rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. RESULTS: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). CONCLUSIONS: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk factor was pre-existent coronary or peripheral artery disease.

The incidence of second tumours and mortality in pituitary adenoma patients treated with postoperative radiotherapy versus surgery alone.

BACKGROUND AND PURPOSE: To assess and compare the incidence of intra- and extracranial tumours and mortality in pituitary adenoma patients treated with postoperative radiotherapy and surgery alone. PATIENTS AND METHODS: A total of 462 pituitary adenoma patients were treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands. Postoperative radiotherapy was administered on indication in 236 patients. RESULTS: The median follow-up time was 14 (range 1-49) years in patients treated with radiotherapy and 6 (range 1-34) years in patients treated with surgery alone. Three radiotherapy patients developed an intracranial tumour compared to one patient treated with surgery alone. The numbers of extracranial tumours per follow-up year were 6.5 (95% CI 2.5-10.5) and 5.1 (95% CI 1.9-8.2) in patients treated with and without a technique with vertex field and central body axis irradiation and 7.1 (CI 95% 2.9-11.2) in surgery alone patients. Forty-five patients treated with radiotherapy died compared to twenty-four patients treated with surgery alone (log-rank test RR 1.26, 95% CI 0.77-2.08, p=0.36). CONCLUSION: In this study postoperative radiotherapy and a radiotherapy treatment technique with vertex field and central body axis irradiation were not associated with an increased incidence of second tumours and mortality in pituitary adenoma patients.

18F-FLT-PET for detection of rectal cancer.

PURPOSE: This pilot study was undertaken to examine the ability of (18)F-3'-fluoro-3'-deoxy-l-thymidine positron emission tomography ((18)F-FLT-PET)to detect rectal cancer, to identify pathologic lymph nodes and to determine the accuracy of tumour length estimation in comparison with computer tomography (CT). METHODS: Nine patients with biopsy proven rectal cancer underwent CT and (18)F-FLT-PET scanning prior to short-term pre-operative radiotherapy (5×5Gy). Within 10 days after the start of radiotherapy a surgical resection was performed. Tumour lengths and regional lymph node visualisation on both imaging modalities were compared with pathology findings. RESULTS: All tumours were visible on CT. (18)F-FLT-PET visualised 7 out of 9 tumours (78%). The pathology-based tumours lengths correlated better with CT as compared to FLT-PET(r=0.91, p<0.01). (18)F-FLT-PET was not able to visualise pathologic lymph nodes. However, CT identified all patients with pathologic lymph nodes. CONCLUSION: Primary rectal cancer can be visualised by (18)F-FLT-PET in the majority of cases but not in all. However, (18)F-FLT-PET was not able to identify pathologic lymph nodes. Therefore, we conclude that (18)F-FLT-PET has limited value for the detection of pathologic lymph nodes and tumour delineation in rectal cancer.

Detection of local, regional, and distant recurrence in patients with psa relapse after external-beam radiotherapy using (11)C-choline positron emission tomography.

PURPOSE: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of (11)C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). METHODS AND MATERIALS: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq (11)C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. RESULTS: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for (11)C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. CONCLUSIONS: (11)C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.

Iris metastasis in small-cell lung carcinoma.

Small-cell lung cancer (SCLC) is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic treatment, until now treatments have failed to control or cure this disease in most patients. Here, we describe a patient with SCLC in which symptoms caused by iris metastasis were the only sign of relapse after multimodality treatment.

Radiotherapy is not associated with reduced quality of life and cognitive function in patients treated for nonfunctioning pituitary adenoma.

PURPOSE: To assess the influence of different treatment modalities on long-term health-related quality of life (HR-QoL) and cognitive problems among patients who had been treated for nonfunctioning pituitary adenoma (NFA). METHODS AND MATERIALS: Eighty-one patients (49 men and 32 women, aged 55 +/- 10 years) with a minimal follow-up period of 1 year after treatment for NFA participated in this cross-sectional study. Sixty-two patients were initially treated by transsphenoidal surgery and 19 by craniotomy. Subsequently, 45 of these 81 subjects (56%) received additional radiotherapy (RT) after surgery because of a tumor remnant or regrowth. All subjects filled in standardized questionnaires measuring HR-QoL, depression, fatigue, and cognitive problems. RESULTS: Patients who underwent additional RT more frequently underwent a craniotomy and were younger at surgery, but not at entering this study. They also used more hormonal substitution. Most HR-QoL domains showed a similar score in patients who underwent RT when compared with patients who did not receive RT. However, vitality and physical functioning proved to be better in RT subjects, and RT subjects also had better scores for depression and physical and mental fatigue (all p < 0.05). Some aspects of HR-QoL of patients who have been successfully treated for NFA are reduced compared with the normal population, but this was much more pronounced in the group that did not receive RT. In multivariate analysis, RT remained significantly associated with improved HR-QoL. No differences in cognitive function scores were observed. CONCLUSION: Postoperative RT in patients with NFA is not associated with reduced quality of life or cognition when compared with surgery alone.