Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

Background: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD)

Abstract Background: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. Methods: Multicentre, open-label study in untreated patients 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 þ R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. Results: Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WTRAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab- FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WTRAS: 26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6e1.5]; WT-RAS:13/15; HR: 0.7 [0.4 e1.3]). Median OS was 37/41 months (HR:1.0 [0.6e1.8]; WT-RAS: 39/49; HR:0.9 [0.4 e1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS 30%/ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p Z 0.003) and neuropathy (13%/0%; p Z 0.025) in the Pmab-FOLFOX4 arm. Conclusions: In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov:NCT00885885

SEOM-GECOD clinical guideline for unknown primary cancer (2021).

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity

Primary and secondary tumors of the peritoneum: key imaging features and differential diagnosis with surgical and pathological correlation

Abstract Peritoneal malignancies represent a diagnostic challenge for abdominal radiologists, oncologists, surgeons and pathologists in multidisciplinary teams, who must address their differential diagnosis, staging and treatment. In this article, we explain the pathophysiology of these processes and lay out the role of different imaging techniques in their evaluation. Then, we review the clinical and epidemiological aspects, the main radiological features and the therapeutic approaches for each primary and secondary peritoneal neoplasm, with surgical and pathological correlation. We further describe other rare peritoneal tumors of uncertain origin and a variety of entities that may mimic peritoneal malignancy. Finally, we summarize the key imaging findings of each peritoneal neoplasm to facilitate an accurate differential diagnosis that may impact patient management. Clinical relevance statement Imaging plays an essential role in the evaluation of peritoneal malignancies, assessing their extension, detecting unfavorable sites of involvement and facilitating an accurate differential diagnosis, helping to choose the best therapeutic approach. Graphical abstrac

Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial.

Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. In total, 101 patients were followed for a median of 12 (6-17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD)

Abstract Background: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. Methods: Multicentre, open-label study in untreated patients 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 þ R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. Results: Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WTRAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab- FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WTRAS: 26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6e1.5]; WT-RAS:13/15; HR: 0.7 [0.4 e1.3]). Median OS was 37/41 months (HR:1.0 [0.6e1.8]; WT-RAS: 39/49; HR:0.9 [0.4 e1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS 30%/ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p Z 0.003) and neuropathy (13%/0%; p Z 0.025) in the Pmab-FOLFOX4 arm. Conclusions: In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov:NCT00885885