Resection of Recurrent Pancreatic Cancer: Who Can Benefit?

<b><i>Background:</i></b> Recurrence after resection of pancreatic cancer occurs in up to 80% of patients in the first 2 years after complete resection. While most patients are not eligible for surgical treatment due to disseminated disease, a certain group of patients can be evaluated for re-resection of local recurrence. This review summarizes the current literature on surgical treatment of recurrent pancreatic cancer and potential prognostic factors. <b><i>Summary:</i></b> Re-resection of recurrent pancreatic cancer provides a significant survival benefit to selected patients with acceptable procedure-related mortality. Median overall survival after re-resection of recurrent pancreatic cancer is up to 28 months. The most relevant clinical parameters associated with a prognostic benefit are young patient age (&#x3c;65 years), time to initial resection (&#x3e;10 months), and preoperative chemotherapy before re-resection. Molecular markers are currently under investigation and might help to improve patient selection in the future. <b><i>Key Message:</i></b> Re-resection of recurrent pancreatic cancer is safe and feasible in experienced hands. Selected patients benefit from surgical treatment, but future studies are needed to identify reliable prognostic markers predicting survival.

Re-Irradiation With Stereotactic Body Radiotherapy for In-Field Recurrence of Pancreatic Cancer After Prior Stereotactic Body Radiotherapy: Analysis of 24 Consecutive Cases

Purpose/ObjectivesLocally recurrent pancreatic cancer is a therapeutic challenge, and aggressive approaches are needed to improve its clinical outcomes. Stereotactic body radiotherapy (SBRT) is a promising treatment for pancreatic cancer with an excellent local control and acceptable toxicity. However, the safety and efficacy of SBRT for in-field recurrence after initial SBRT remain unknown. The aim of the study was to investigate the feasibility of re-irradiation with SBRT for locally recurrent pancreatic cancer after prior definitive SBRT.Material/MethodsTwenty-four consecutive patients with pancreatic cancer received two courses of SBRT in our center between January 2014 and December 2016. The median prescription dose of the initial and second courses of SBRT was 35.5 Gy/5–7f and 32 Gy/5–8f, respectively. Clinical outcomes including overall survival (OS), disease control, and toxicity were evaluated after treatment.ResultsThe median interval between two courses of SBRT was 13 months (range: 6–29 months). From the first SBRT, the median OS of 18 patients with limited diseases was 26 months (95% CI: 19.1–32.95 months). The median OS of 12 patients without metastasis was 14 months (95% CI: 10.6–17.4 months) from re-irradiation of SBRT. The overall response rate and disease control rate were 50% and 13%, and 100% and 86.9% after each SBRT, respectively. Carbohydrate antigen 19-9 (CA19-9) levels declined dramatically after re-irradiation within 1 month (p = 0.002) and 3 months (p = 0.028). Twelve (75%) out of 16 patients had pain relief after re-irradiation. None of the patients experienced gastrointestinal toxicity.ConclusionsRe-irradiation with SBRT can provide favorable outcomes and effective analgesia with mild toxicity after prior SBRT for in-field recurrent pancreatic cancer, which might be feasible for locally relapsed pancreatic cancer.

Carbon ion radiotherapy as definitive treatment in locally recurrent pancreatic cancer

Purpose Data on management of locally recurrent pancreatic cancer (LRPC) after primary resection are limited. Recently, surprisingly high overall survival rates were reported after irradiation with carbon ions. Here, we report on our clinical experience using carbon ion radiotherapy as definitive treatment in LRPC at the Heidelberg Ion-Beam Therapy Center (HIT). Methods Between 2015 and 2019, we treated 13 patients with LRPC with carbon ions with a median total dose of 48 Gy (RBE) in 12 fractions using an active raster-scanning technique at a rotating gantry. No concomitant chemotherapy was administered. Overall survival, local control, and toxicity rates were evaluated 18 months after the last patient finished radiotherapy. Results With a median follow-up time of 9.5 months, one patient is still alive (8%). Median OS was 12.7 months. Ten patients (77%) developed distant metastases. Additionally, one local recurrence (8%) and two regional tumor recurrences (15%) were observed. The estimated 1‑year local control and locoregional control rates were 87.5% and 75%, respectively. During radiotherapy, we registered one gastrointestinal bleeding CTCAE grade III (8%) due to gastritis. The bleeding was sufficiently managed with conservative therapy. No further higher-grade acute or late toxicities were observed. Conclusion We demonstrate high local control rates in a rare cohort of LRPC patients treated with carbon ion radiotherapy. The observed median overall survival rate was not improved compared to historical in-house data using photon radiotherapy. This is likely due to a high rate of distant tumor progression, highlighting the necessity of additional chemotherapy.

Impact of FAPI-PET/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer

(1) Background: A new radioactive positron emission tomography (PET) tracer uses inhibitors of fibroblast activation protein (FAPI) to visualize FAP-expressing cancer associated fibroblasts. Significant FAPI-uptake has recently been demonstrated in pancreatic cancer patients. Target volume delineation for radiation therapy still relies on often less precise conventional computed tomography (CT) imaging, especially in locally recurrent pancreatic cancer patients. The need for improvement in precise tumor detection and delineation led us to innovatively use the novel FAPI-PET/CT for radiation treatment planning. (2) Methods: Gross tumor volumes (GTVs) of seven locally recurrent pancreatic cancer cases were contoured by six radiation oncologists. In addition, FAPI-PET/CT was used to automatically delineate tumors. The interobserver variability in target definition was analyzed and FAPI-based automatic GTVs were compared to the manually defined GTVs. (3) Results: Target definition differed significantly between different radiation oncologists with mean dice similarity coefficients (DSCs) between 0.55 and 0.65. There was no significant difference between the volumes of automatic FAPI-GTVs based on the threshold of 2.0 and most of the manually contoured GTVs by radiation oncologists. (4) Conclusion: Due to its high tumor to background contrast, FAPI-PET/CT seems to be a superior imaging modality compared to the current gold standard contrast-enhanced CT in pancreatic cancer. For the first time, we demonstrate how FAPI-PET/CT could facilitate target definition and increases consistency in radiation oncology in pancreatic cancer.

Repeated Pancreatectomy for Isolated Local Recurrence in the Remnant Pancreas Following Radical Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Pooled Analysis

The mainstream treatment for recurrent pancreatic cancer is potent chemotherapy or chemoradiotherapy. However, recent clinical investigations have suggested a potential oncologic role of local resection of recurrent pancreatic cancer. This systemic review with a pooled analysis aimed to assess the potential role of local repeated pancreatectomy with respect to the survival outcomes for patients with recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. The PubMed database was searched, and 15 articles reporting on repeated pancreatectomy for local recurrence of PDAC in the remnant pancreas were identified. The pooled individual data were examined for the clinical outcomes of repeated pancreatectomy for recurrent PDAC. The survival analysis was performed using the Kaplan–Meier method. In the pooled analysis, the mean time interval from initial pancreatectomy to repeated pancreatectomy was 41.3 months (standard deviation (SD), 29.09 months). Completion total pancreatectomy was most commonly performed as repeated pancreatectomy (46 patients, 92.0%), and partial pancreatic resection was performed for only 4 (10.3%) patients. Twenty (40.9%) patients received postoperative chemotherapy following repeated pancreatectomy. The median overall survival was 60 months (95% confidential interval (CI): 45.99–74.01) after repeated pancreatectomy for isolated local recurrence in the remnant pancreas. Overall survival was markedly longer considering the timing of the initial pancreatectomy for pancreatic cancer (median, 107 months (95% CI: 80.37–133.62). The time interval between the initial and subsequent repeated pancreatectomy for pancreatic cancer was not associated with long-term oncologic outcomes (p = 0.254). Repeated pancreatectomy cannot completely replace adjuvant chemotherapy but should be considered for patients with isolated local recurrent PDAC in the remnant pancreas.