Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.
TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.
e16548 Background: There is scarce information on the efficacy of low-dose enzalutamide in metastatic castration-resistant prostate cancer. We report on a series treated with half dose enzalutamide. Methods: We observed a trend in our practice to initiate low-dose enzalutamide at the time of disease progression in older patients considered frail, presenting with cardio-vascular comorbidity or with history of neurological symptoms. Records were retrospectively reviewed. The selection criteria were: 1) Metastatic disease demonstrated by at least one imaging modality, CT, bone scan, or positron emission tomography. 2) Progression of prostate specific antigen (PSA). 3) Castrate testosterone level ( < 0.2 ng/mL). 4) Enzalutamide treatment at 80 mg or less, once daily. To estimate the rate of PSA response, we used linear interpolation to compute the time from the initiation of low-dose enzalutamide to 50% PSA reduction. Results: Between November 2015 and December 2018 at the Martinique University Hospital, 10 patients matching the selection criteria were treated with ≤ 80 mg enzalutamide od: 8 started de novo with the low dose, 2 started with 160 mg but required dose reduction for intolerance. The mean age was 78 years (range 67-84). Three had painful bone metastases. The mean PSA at start of low dose enzalutamide was 88 ng/mL (range 1.06 - 251.8). All patients were maintained with reduced dose. At the current follow-up of 9 months (range 0 - 36 months), PSA response was observed in 7 patients ( = 70%), 1 was not evaluable (PSA not assessed), 2 did not respond. Of the 2 non-responders, one had no sign or symptom of disease progression; the other presented with extensive disease progression previously treated with abiraterone, he refused to receive increased dose enzalutamide. Among the 7 responders, the time to 50% PSA reduction was 57 days (range 26 - 119). Currently, the decline of PSA remains sustained in 6 of the 7 responders, it increased in 1 who discontinued enzalutamide. Pain decreased in the 3 symptomatic patients, including the PSA non-responder. Conclusions: Low dose enzalutamide appears efficient in a large proportion of selected frail patients. Further follow-up is required to evaluate the long-term response.
This retrospective-observational study hypothesizes that preoperative 18FDG-PET for breast cancer has significant prognostic value for the prediction of survival. Data from patients who had breast surgery and had a preoperative FDG-PET examination at the UZ Brussel in 2002-2008 and in 2009-2015 will be analyzed without restriction on age or sex. Data collection for the cohort 2002-2008 has been finalized and will be shared on Mendeley (Reserved DOI: 10.17632/sfvtmrd8z9.1 ). Data for the cohort 2009-2015 will be collected by end of 2020. Detailed and referred to in: # Breast cancer preoperative 18FDG-PET, overall survival prognostic separation compared with the lymph node ratio. # Vinh-Hung V, Everaert H, Gorobets O, Van Parijs H, Verfaillie G, Vanhoeij M, Storme G, Fontaine C, Lamote J, Perrin J, Farid K, Nguyen NP, Verschraegen C, De Ridder M. # Breast Cancer. 2021 Jul;28(4):956-968. doi: 10.1007/s12282-021-01234-z # PMID: 33689151 https://link.springer.com/article/10.1007%2Fs12282-021-01234-z # Is there a utility of [18F]FDG-PET before surgery in breast cancer? A 15-years overall survival analysis. # Perrin, Farid K, Van Parijs H, Gorobets O, Vinh-Hung V, Nguyen NP, Djassemi N, De Ridder M, Everaert H. # World J Clin Oncol. Pending. Study registration: https://www.isrctn.com/ISRCTN17962845
Purpose: To evaluate the survival effects due to adjuvant radiotherapy for early breast cancer, when follow-up time of the studies increases. Materials and Methods: Time-lapse and cohort analysis of the trials / results published by Cuzick (Cancer Treat Rep 1987) and the EBCTCG (Oxford 1990, N Engl J Med 1995, Lancet 2000) of the unconfounded radiotherapy trials (surgery (S) versus same surgery plus radiotherapy (SRT)). Details on begin year, number of patients and fraction dose used in the trial are presented, as well as analysis of trials with increased (i.e. increase higher than overall) or not increased (i.e. increase lower than overall or decrease) non-breast-cancer mortality (radiotherapy versus control). Results: The table shows odds ratios/P-values (SRT versus S) for overall survival. The first column (C1) refers to the publication of which the O-E and Var are borrowed (logrank statistics) to calculate the overall odds ratio (OR) of the selected group of trials. C2: overall pure OR of the trials in the paper. C3: pure OR in the subsequent papers of the cohort of eight trials in the Cuzick analysis. Gain in OR of recent versus old trials: C4: overall results (cutoff 1970); C5: cohort of 36 trials of NEJM paper (cutoff 1970) and C6: NEJM cohort (cutoff 1975). Gain in OR of large trials (>600 pts) versus small (<600) trials: C7: all trials; C8: cohort of 36 trials of NEJM paper. C9: combined pure OR of both recent and large (>1970 and >600 pts) trials. Combined pure OR of all either old or small (<=1970 or <600 pts) trials: C10: all trials; C11: cohort of six old or small Cuzick trials. Gain in OR due to using classical fraction dose (1.8-2.0 Gy/f) versus other: C12: all trials with known fraction dose; C13: NEJM cohort. Combined pure OR of all trials with high (C14) or low (C15) non-breast-cancer mortality (NBC) due to irradiation (compared to overall NBC; reference = Lancet paper). C16: combined pure OR of trials without specified NBC in the Lancet paper (i.e. the small trials). There was a correlation between old trials and high NBC, and between small trials and high NBC. The oldest cohort of trials (Cuzick) does not show an important improvement of results if follow-up time decreases, neither does the more recent cohort (NEJM) shows a deterioration if follow-up time increases. The results of the EBCTCG update (Sept. 2000, Oxford, to be published) are in agreement with the above presented results. Conclusion: Update and cohort analysis of overall survival OR (SRT versus S) do not show large changes in the clinical effects, but a systematic increase of the statistical significance is present as follow-up increases. Begin year of trial, number of patients in the trial and fraction dose become more significant at each update. The results of subgroups of trials following effect of radiotherapy on non-breast-cancer mortality remain stable and strengthen the hypothesis that the seemingly benefit in the recent trials is not only due to short follow-up, but is an inherent characteristic of the recent and large trials, independent of follow-up time. The overall survival benefit of adjuvant radiotherapy in case present radiotherapy techniques (preventing normal tissue toxicity, with classical fractionation) are used, becomes more apparent. Tabled 112345678910111213141516Cuzick 19871.02/0.31.02/0.30.88/0.20.94/0.50.86/0.11.04/0.31.04/0.30.91/0.51.06/0.20.88/0.081.18/0.4Oxford 19900.99/0.81.01/0.80.90/0.10.98/0.80.89/0.21.01/0.71.04/0.40.93/0.51.06/0.30.90/0.090.96/0.6N Engl J Med 950.97/0.30.98/0.50.91/0.070.91/0.070.94/0.20.89/0.030.89/0.030.86/6E-31.02/0.51.01/0.80.88/0.050.88/0.021.02/0.70.88/2E-31.06/0.3Lancet 20000.96/0.061.00/0.90.90/0.010.88/6E-30.87/2E-30.86/8E-40.86/9E-40.85/2E-41.02/0.41.03/0.40.86/4E-30.86/5E-31.03/0.40.87/2E-51.06/0.3 Open table in a new tab
