Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R.

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.

Detection rate, pattern of relapse and influence on therapeutic decision of PSMA PET/CT in patients affected by biochemical recurrence after radical prostatectomy, a retrospective case series

Aims 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported. Results 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003). Conclusions PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging (AU)

Detection rate, pattern of relapse and influence on therapeutic decision of PSMA PET/CT in patients affected by biochemical recurrence after radical prostatectomy, a retrospective case series.

AIMS: 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported. RESULTS: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003). CONCLUSIONS: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.

Critical appraisal of the role of volumetric modulated arc therapy in the radiation therapy management of breast cancer.

BACKGROUND: The aim of this review is the critical appraisal of the current use of volumetric modulated arc therapy for the radiation therapy management of breast cancer. Both clinical and treatment planning studies were investigated. MATERIAL AND METHODS: A Pubmed/MEDLINE search of the National Library of Medicine was performed to identify VMAT and breast related articles. After a first order rejection of the irrelevant findings, the remaining articles were grouped according to two main categories: clinical vs. planning studies and to some sub-categories (pointing to significant technical features). Main areas of application, dosimetric and clinical findings as well as areas of innovations were defined. RESULTS: A total of 131 articles were identified and of these, 67 passed a first order selection. Six studies reported clinical results while 61 treatment dealed with treatment planning investigations. Among the innovation lines, the use of high intensity photon beams (flattening filter free), altered fractionation schemes (simultaneous integrated boost, accelerated partial breast irradiation, single fraction), prone positioning and modification of standard VMAT (use of dynamic trajectories or hybrid VMAT methods) resulted among the main relevant fields of interest. Approximately 10% of the publications reported upon respiratory gating in conjunction with VMAT. CONCLUSIONS: The role of VMAT in the radiation treatment of breast cancer seems to be consolidated in the in-silico arena while still limited evidence and only one phase II trial appeared in literature from the clinical viewpoint. More clinical reports are needed to fully proove the expected dosimetric benefits demonstrated in the planning investigations.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Exploratory Analysis on Overall Survival after Either Surgery or Stereotactic Radiotherapy for Lung Oligometastases from Colorectal Cancer.

AIMS: Lung metastasectomy and, more recently, stereotactic body radiotherapy (SBRT), are frequently proposed to stage IV oligometastatic colorectal cancer (CRC) patients. In the absence of a randomised comparison between the two treatments, we aimed to retrospectively explore the effect on overall survival and progression-free survival (PFS) in a comparative cohort study. MATERIALS AND METHODS: We included patients who consecutively underwent surgery (n = 142) or SBRT (n = 28) as first local therapy at the time of lung progression, between 2005 and 2012. Both overall survival and PFS functions according to treatment were calculated using the Kaplan-Meier method and compared using the Log-rank test. The effect of treatment on overall survival and PFS was estimated by Cox models using different adjustment methods. RESULTS: Patients receiving SBRT were older and were treated more recently, whereas the two cohorts were similar for most baseline prognostic factors. Overall survival at 1 and 2 years was 0.89 and 0.77 for SBRT and 0.96 and 0.82 for surgery (P = 0.134), respectively. Multivariable analyses did not highlight a clear treatment effect on overall survival (adjusted hazard ratioSBRT versus surgery = 1.71; 95% confidence interval 0.82-3.54; P = 0.149) and even smaller differences using the inverse probability treatment weighting method (hazard ratioSBRT versus surgery = 1.28, 95% confidence interval 0.58-2.82; P = 0.547). The results of PFS were unreliable because different follow-up protocols were applied in the two cohorts. CONCLUSION: With limitations consisting in the retrospective observational design and different sample sizes, the results of this explorative analysis indicate that overall survival probability after SBRT is similar to surgery for the first 2 years from treatment. This finding supports the need for high-quality trials comparing different treatment modalities for lung oligometastases from CRC.

Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study.

PURPOSE: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). METHODS: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1ß, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared. RESULTS: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1ß, TGF-α, TNF-α, VEGF. CONCLUSIONS: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.

Using PET-CT in the restaging of primitive mediastinal B-cell lymphoma (PMBCL) after chemotherapy: which criteria should we use?

AIM: Primitive mediastinal B-cell lymphoma (PMBCL) is a relatively rare form of non-Hodgkin lymphoma (NHL), typically concerning the youngster, with an aggressive course and poor prognosis. The therapy generally consists of high dose chemotherapy followed by radiotherapy. PET-CT is used at staging, restaging after chemotherapy and after radiotherapy, or when relapse is suspected. Aim of the study was to compare different criteria in the evaluation of response to chemotherapy in this setting. METHODS: Thirty-eight patients with PMBCL (15 M, 23 F, median age 33 yrs [range 18-79]), all treated with chemo-immunotherapy and radiotherapy, who had undergone baseline (b-PET) and end of chemotherapy (f-CHT-PET) 18F-FDG-PET-CT scans at our institution between July 2004 and September 2014 were retrospectively re-evaluated; the median follow-up was 42 months (range 4-109), at which 4/38 (11%) had died, 5/38 (13%) were in partial response (PR) and 29/38 (76%) were in complete response (CR). The primary endpoint was progression-free survival (PFS), while the secondary one was overall survival (OS), according to the Cheson criteria. SUV max of the mediastinal disease mass at staging, of the residual mass at CT after chemo-immunotherapy, SUV max of the liver and of the mediastinal blood pool (MBP) were calculated for all patients. RESULTS: In our population, we observed that: 1) visual criteria performs better when positivity-negativity threshold is set at point 3 of the 5-point scale (5-PS); 2) semiquantitative approach by use of Δ SUV max performs better when the threshold is set at 66% decrease: in fact, at Δ SUV max analysis with 66% decrease, 9 patients resulted positive at the test (Δ SUV max ≤66%), 29 negative (Δ SUV max >66%). CONCLUSION: In our population Δ SUV max could be working well in these patients because the baseline values are very high and very homogeneous. Our data, though limited in numerosity of patients and events, suggests that in this particular setting the use of the 5-PS reporting system could not be the best tool available; on the other hand, Δ SUV max could prove to be reliable in the evaluation of response to chemotherapy.

The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): a survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer.

PURPOSE: Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients. STUDY DESIGN: During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed. RESULTS: A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed. CONCLUSIONS: Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.