Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available ...about the criteria to candidate patients to resection after CT.
Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3–6months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery.
Median survival (MS) for the whole population was 18.3months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0months) as compared with 162 non-resected patients (16.5months) (P<0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction>50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5months,P=0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9months,P=0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3–T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival.
CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.
•ESCAPE investigates PET/MRI biomarkers to predict response for esophageal cancer.•The study focused on tumor regression/ERI assessed by T2 MRI during and after nCRT.•Data referred to 25 patients (30 ...enrolled) showed relevant regression in most patients.•ERImid identified complete responders with AUC = 0.78 (0.93, combined with Vpre)•ERImid is a promising predictor of response, with intrinsically high usability.
The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI.
From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2–6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR.
Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results.
Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.
Aim
The aim of this study was to assess the value of positron emission tomography (PET)/CT and sentinel lymph node (SLN) biopsy in staging inguinal lymph nodes in anal cancer patients and to ...determine if the results of the two methods could be of prognostic value.
Method
Sixty‐three patients with anal cancer and clinically negative inguinal lymph nodes underwent lymphoscintigraphy and inguinal SLN biopsy and/or fluorodeoxyglucose (FDG) PET/CT scan. All patients were treated with radiotherapy combined with 5‐fluorouracil and mitomycin‐C.
Results
Overall (OS) and disease‐free survival (DFS) were 43 months (range 5–211) and 43 months (range 4–142) respectively. PET/CT examination showed high FDG uptake in the inguinal lymph nodes in 25% of patients. Thirty‐five patients with inguinal uptake at lymphoscintigraphy underwent inguinal SLN biopsy and metastatic nodes were found in 31.4%. There was no statistical difference in OS (55 vs 41 months; P = 0.652) and DFS (48 vs 38 months; P = 0.992) between the group which showed inguinal uptake on PET/CT and the group which did not, while a positive inguinal SLN was associated with a worse OS (28 vs 59 months; P = 0.028) and DFS (56 vs 21 months; P = 0.046). When the two examinations were compared PET/CT showed a sensitivity, specificity, positive predictive value and negative predictive value of 22%, 82%, 33% and 73% respectively.
Conclusion
The technique of SLN biopsy had a better diagnostic accuracy than total body FDG‐PET/CT for the staging of inguinal lymph nodes in anal cancer patients; moreover it was a stronger predictor of OS and DFS than PET/CT.
To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in ...locally advanced rectal cancer (LARC).
Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6–8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR.
Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10−16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%).
MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.
•An additional MRI performed during CRT may be useful in the early evaluation of response to CRT.•TRG correlated slightly better with ΔVmid (ρ=0.713, p<0.001) than ΔVpost (ρ=0.645, p<0.001).•MidMRI might be potentially useful to tailor patient’s treatment in relation to tumour shrinkage.
To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative ...parameters can predict response to treatment.
Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5 T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders “non-GR” (TRG 0–2) and good responders “GR” (TRG 3–4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann–Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis.
Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness <3.635 was able to predict GR with an area under the ROC curve (AUC) of 0.988, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Ve kurtosis <21.095 was able to predict response with an AUC of 0.963, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Other parameters were not different between groups or predictors of response.
Ve skewness and kurtosis seem to be promising in the prediction of response to CRT in rectal cancer patients.
•Rectal cancer's perfusion heterogeneity at DCE-MRI assessed pre-CRT may give information about tumor chemioradiosensitivity.•Skewness and kurtosis of Ve are significantly higher in poor responders than in good responders (p=0.003 and p=0.011).•Poor and good responders resulted not significantly different in term of heterogeneity of ktrans values' distribution.
Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. ...Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples.
We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content TC, < 2 mm
tumor surface area TSA, DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable.
Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm
tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for
amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection.
Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies.
Anti-PD-1 and PD-L1 (collectively PD-L1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden ...(TMB) may improve benefit prediction.
Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients.
Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-L1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio aHR 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low.
The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.
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