Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study.

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.

Stereotactic body radiation therapy in unresectable stage III non-small cell lung cancer: A systematic review.

In unresectable stage III non-small cell lung cancer (NSCLC), the standard of care for most fit patients is concurrent chemotherapy with normofractionated radiotherapy (NFRT), followed by durvalumab consolidation. Nevertheless, almost half of patients will present locoregional or metastatic intrathoracic relapse. Improving locoregional control thus remains an important objective. For this purpose, stereotactic body radiotherapy (SBRT) may be a relevant treatment modality. We performed a systematic review of the literature that evaluate the efficacy and safety of SBRT in this situation, either instead of or in addition to NFRT. Among 1788 unique reports, 18 met the inclusion criteria. They included 447 patients and were mainly prospective (n = 10, including 5 phase 2 trials). In none, maintenance durvalumab was administered. Most reported SBRT boost after NFRT (n = 8), or definitive tumor and nodal SBRT (n = 7). Median OS varied from 10 to 52 months, due to the heterogeneity of the included populations and according to treatment regimen. The rate of severe side effects was low, with <5 % grade 5 toxicity, and mainly observed when mediastinal SBRT was performed without dose constraints to the proximal bronchovascular tree. It was suggested that a biologically effective dose higher than 112.3 Gy may increase locoregional control. SBRT for selected stage III NSCLC bears potential to improve loco-regional tumor control, but at present, this should only be done in prospective clinical trials.

Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection.

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Focal Photocoagulation as an Adjunctive Therapy to Reduce the Burden of Intravitreal Injections in Macula Edema Patients, the LyoMAC2 Study.

AIM: To assess the efficacy of focal photocoagulation of capillary macroaneurysms (CMA) to reduce the burden of intravitreal injections (IVI) in patients with macular edema (ME). MATERIALS AND METHODS: Retrospective multicenter study in patients with diabetic ME or ME secondary to retinal vein occlusion (ME-RVO). CMA associated with ME were selectively photocoagulated. Patients were followed for one year after photocoagulation. RESULTS: 93 eyes of 76 patients were included in this study. At 6 months after the laser (n = 93), there was a significant decrease in mean macular thickness (from 354 µm to 314 µm, p < 0.001) and in mean IVI number (from 2.52 to 1.52 at 6 months, p < 0.001). The mean BCVA remained stable (0.32 and 0.31 logMAR at baseline and 6 months, p = 0.95). At 12 months (n = 81/93), there was a significant decrease in mean macular thickness (from 354 µm to 314 µm, p < 0.001) and in mean IVI number (from 4.44 to 2.95 at 12 months, p < 0.001), while the mean BCVA remained stable (0.32 and 0.30 logMAR at baseline and 12 months, p = 0.16). CONCLUSION: Focal laser photocoagulation of CMA seems to be effective and safe for reducing the burden of IVI in patients with ME. Their screening during the follow-up should be considered closely.

Surgical resection versus transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. METHODS: Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage A Child-Pugh A HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. RESULTS: Ninety-eight patients underwent SR and 62 were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3­Gy fractions. Median OS follow-up was 93 months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1­year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with a median OS of 37 vs. 63 months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, a significant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by 42 (42.9%) SR and 19 (30.6%) TACE-hRT patients (p = 0.17). CONCLUSION: In patients presenting Child-Pugh A BCLC­A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.

Real World Data of Diagnosis, Survival, and Treatment Outcomes in Patients With Metastatic Non Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Metastatic non clear cell renal cell carcinoma (nccRCC) is an heterogenous group, usually excluded from phase 3 trials. We report real life data of prognosis and systemic management of those patients. METHODS: We retrospectively included 102 metastatic nccRCC patients (unspecified papillary, n = 10; type 1 and 2 papillary n = 10 and n = 32; translocation RCC, n = 9; chromophobe, n = 14; collecting duct, n = 14) treated between 2006 and 2020. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Among patients who underwent pathological review, 40.8% presented a complete histological discordance. First line treatments were mainly tyrosine kinase inhibitor (60.8%), combination including immunotherapy (7.8%) or combination of chemotherapy (13.7%). Median ORR ranged from 0% in unspecified papillary RCC to 42.9% in type 1 papillary RCC. Median PFS ranged from 2.9 months in collecting duct carcinoma to 10.9 months in type 1 papillary RCC. Median OS ranged from 6.8 months in collecting duct carcinoma to 29.1 months in MiT family translocation RCC. Thirty (29.4%) patients were included in a treatment trial during their treatment course. CONCLUSION: Metastatic nccRCC patients have variable prognosis due to heterogeneity of histological subtypes. Their diagnosis and access to therapeutic innovation remain suboptimal. Dedicated prospective trials are needed.

Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review.

BACKGROUND: Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may improve results of this therapeutic option. The role of this review was to report the clinical results of photon- and particle-based EBRT in unresectable STS. MATERIAL AND METHODS: We performed a systematic review of the literature on Pubmed database to identify studies investigating the efficacy and safety of EBRT. The primary endpoint was local control (LC) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events in a subset of patients with gross disease STS. RESULTS: We identified 29 studies involving 1409 patients (pts) evaluating photon (n = 18; 956 pts), proton (n = 1; 21 pts), carbon ion (n = 2; 152 pts), neutron (n = 7; 259 pts) or pion (n = 1; 21 pts) therapy. Definitive EBRT achieves valuable 5-year LC rates of 28-73% with photon and 52-69% with particle therapies. Most local failures (66-100%) occurred within 3 years. Long-term disease control can be achieved in a fraction of patients, with 5-year PFS and OS of 0-39% and 24.7-63%, respectively. The rate of severe adverse events was highly variable with photons, <15% in proton and carbon ion therapy, whereas 25 to 50% of patients treated with neutrons and pions presented severe AE. While a dose higher or equal 64 Gy seem to improve the prognosis, delivering a dose higher or equal 68 Gy dramatically increases severe adverse events. CONCLUSION: Definitive EBRT with dose 64-66 Gy seems to be a safe and efficient treatment for unresectable STS. Future clinical trials should assess the potential of biomarkers of response, thus identifying patients that could benefit from local treatment.

Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma.

INTRODUCTION: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes. METHODS: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype. RESULTS: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR -18-+18), +8% (IQR 0-+24), -12% (IQR -20-3) and -11% (IQR -15-9), respectively (p = 0.001). Median viable cells were 10%, 60%, 20% and 70% (p = 0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p = 0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect. CONCLUSION: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns.