RESUMEN
Introduction: Patients with localized pancreatic adenocarcinoma (PDAC) benefit from multi-modality therapy. Whether care patterns and oncologic outcomes vary if a patient was seen through a pancreatic multi-disciplinary clinic (PMDC) versus only individual specialty clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients with localized PDAC from 2019- 2022 who eventually underwent resection. It was our standard practice for borderline resectable (BRPC) patients to undergo ≤4 months of neoadjuvant chemotherapy, ± radiation, followed by exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation and potential exploration. Descriptive and multivariable analyses (MVA) were performed to examine the association between clinic type (PMDC vs individual specialty clinics i.e. surgical oncology, medical oncology, or radiation oncology) and study outcomes. Results: A total of 416 patients met inclusion criteria. Of these, 267 (64.2%) had PMDC visits. PMDC group received radiation therapy more commonly (53.9% versus 27.5%, p=0.001), as compared to individual specialty clinic group. Completion of neoadjuvant treatment (NAT) was far more frequent in patients seen through PMDC compared to patients seen through individual specialty clinics (69.3% vs 48.9%). On MVA, PMDC group was significantly associated with receipt of NAT per institutional standards (adjusted OR 2.23, 95% CI 1.46-7.07, p=0.006). Moreover, the average treatment effect of PMDC on progression-free survival (PFS) was 4.45 (95CI: 0.87-8.03) months. No significant association between overall survival (OS) and clinic type was observed. Discussion: Provision of care through PMDC was associated with significantly higher odds of completing NAT per institutional standards as compared to individual specialty clinics, which possibly translated into improved PFS. The development of multidisciplinary clinics for management of pancreatic cancer should be incentivized, and any barriers to such development should be addressed.
RESUMEN
The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions.
RESUMEN
Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.
RESUMEN
FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage to healthy tissues. Democratizing FLASH RT by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have a substantial impact in global health. Here, we review recent developments in FLASH RT and present perspective on further developments that could facilitate the democratizing of FLASH RT. These include upgrading and validating current technologies that can deliver and measure the FLASH radiation dose with high accuracy and precision, establishing a deeper mechanistic understanding of the FLASH effect, and optimizing dose delivery conditions and parameters for different types of tumors and normal tissues, such as the dose rate, dose fractionation, and beam quality for high efficacy. Furthermore, we examine the potential for democratizing FLASH radioimmunotherapy leveraging evidence that FLASH RT can make the tumor microenvironment more immunogenic, and parallel developments in nanomedicine or use of smart radiotherapy biomaterials for combining RT and immunotherapy. We conclude that the democratization of FLASH radiotherapy represents a major opportunity for concerted cross-disciplinary research collaborations with potential for tremendous impact in reducing radiotherapy disparities and extending the cancer moonshot globally.
Asunto(s)
Neoplasias , Humanos , Neoplasias/radioterapia , Dosificación Radioterapéutica , Fraccionamiento de la Dosis de Radiación , Radioterapia/métodos , Microambiente Tumoral/efectos de la radiaciónRESUMEN
Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti-PD-1 antibody (a-PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a-PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a-PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB+CD8+ T cells, TH1, and TH17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a-PD-1 shortens the distances from PD-1+CD8+ T cells to tumor cells and to PD-L1+ myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.
Asunto(s)
Terapia Neoadyuvante , Neoplasias Pancreáticas , Humanos , Linfocitos T CD8-positivos/patología , Radioinmunoterapia , Receptor de Muerte Celular Programada 1 , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Microambiente TumoralRESUMEN
Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery. Methods: We retrospectively reviewed surgical specimen outcomes, postoperative complications, and local/pelvic control in a large cohort of patients with LARC who underwent neoadjuvant therapy incorporating upfront short-course radiation therapy followed by consolidation chemotherapy. Results: In our cohort of 83 patients who proceeded to surgery, a complete/near-complete mesorectal specimen was achieved in 90 % of patients. This outcome was not associated with the time interval from completion of radiation to surgery. Postoperative complications were acceptably low. Local control at two years was 93.4 % for all patients- 97.6 % for those with low-risk disease and 90.4 % for high-risk disease. Conclusion: Upfront short-course radiation therapy and consolidation chemotherapy is an effective treatment course. Extended interval from completion of short-course radiation therapy did not impact surgical specimen quality.
RESUMEN
Despite advances in treatment and response assessment in locally advanced rectal cancer (LARC), it is unclear which patients should undergo nonoperative management (NOM). We performed a single-center, retrospective study to evaluate post-total neoadjuvant therapy (TNT) circulating tumor DNA (ctDNA) in predicting treatment response. We found that post-TNT ctDNA had a sensitivity of 23% and specificity of 100% for predicting residual disease upon resection, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 47%. For predicting poor tumor regression on MRI, ctDNA had a sensitivity of 16% and specificity of 96%, with a PPV of 75% and NPV of 60%. A commercially available ctDNA assay was insufficient to predict residual disease after TNT and should not be used alone to select patients for NOM in LARC.
Asunto(s)
ADN Tumoral Circulante , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , ADN Tumoral Circulante/genética , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/genética , Neoplasias del Recto/terapia , Estudios Retrospectivos , QuimioradioterapiaRESUMEN
PURPOSE: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum. METHODS AND MATERIALS: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT. RESULTS: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum. CONCLUSIONS: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control.
RESUMEN
Stereotactic body proton radiotherapy (SBPT) has the potential to be an effective tool for treating liver malignancies. While proton therapy enables near-zero exit dose and could improve normal tissue sparing, including liver and other surrounding structures, there are challenges in implementing the SBPT technique for proton therapy, including respiratory motion, range uncertainties, dose regimen, treatment planning, and image guidance. This article summarizes the technical and clinical challenges facing SBPT, along with the potential benefits of SBPT for liver malignancies. The clinical implementation of the technique is also described for the first six patients treated at the Johns Hopkins Proton Therapy Center using liver SBPT.
RESUMEN
Pancreatic cancer is the fourth leading cause of cancer-related death, with nearly 60,000 cases each year and less than a 10% 5-year overall survival rate. Radiation therapy (RT) is highly beneficial as a local-regional anticancer treatment. As anatomical variation is of great concern, motion management techniques, such as DIBH, are commonly used to minimize OARs toxicities; however, the variability between DIBHs has not been well studied. Here, we present an unprecedented systematic analysis of patients' anatomical reproducibility over multiple DIBH motion-management technique uses for pancreatic cancer RT. We used data from 20 patients; four DIBH scans were available for each patient to design 80 SBRT plans. Our results demonstrated that (i) there is considerable variation in OAR geometry and dose between same-subject DIBH scans; (ii) the RT plan designed for one scan may not be directly applicable to another scan; (iii) the RT treatment designed using a DIBH simulation CT results in different dosimetry in the DIBH treatment delivery; and (iv) this confirms the importance of adaptive radiation therapy (ART), such as MR-Linacs, for pancreatic RT delivery. The ART treatment delivery technique can account for anatomical variation between referenced and scheduled plans, and thus avoid toxicities of OARs because of anatomical variations between DIBH patient setups.
RESUMEN
Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease. Radiation therapy may be used in localized ampullary cancer, sometimes in combination with chemotherapy, but there is no high-level evidence to support its utility. Select tumors may be treated surgically. This article describes NCCN recommendations regarding management of ampullary adenocarcinoma.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Neoplasias Duodenales , Humanos , Neoplasias del Conducto Colédoco/diagnóstico , Neoplasias del Conducto Colédoco/terapia , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias PancreáticasRESUMEN
BACKGROUND: While pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon (IMRT) and proton radiotherapy (IMPT). METHODS: Pre-operative IMRT and IMPT plans were generated on 10 RPS patients. The prescription was 25 Gy radiobiological equivalents (GyEs) (radiobiological effective dose of 1.1) to the clinical target volume and 30 GyEs to the margin at risk, all in five fractions. Comparisons were made using student T-tests. RESULTS: The following endpoints were significantly lower with IMPT than with IMRT: mean doses to liver, bone, and all genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. CONCLUSIONS: IMPT maintained target coverage while significantly reducing the dose to adjacent OARs and integral dose compared to IMRT. A prospective trial treating RPS with pre-operative ultra-hypofractionated IMPT at our institution is currently being pursued.
RESUMEN
A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Terapia Neoadyuvante/efectos adversos , Nivolumab/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Vacunación , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
The current preferred standard of care management for patients with locally advanced rectal cancer is total neoadjuvant therapy, in which all chemotherapy and radiotherapy is delivered before surgery. Within this approach, developed in response to persistently high distant failure rates despite excellent local control with preoperative chemoradiotherapy, there remains questions regarding the optimal radiotherapy regimen (short course vs long course) and sequencing of chemotherapy (induction vs consolidation).
Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias del Recto , Humanos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Quimioradioterapia , Terapia NeoadyuvanteRESUMEN
PURPOSE: Proactive nutrition screening and intervention is associated with improved outcomes for patients with pancreatic adenocarcinoma (PDAC). To better optimize nutrition amongst our PDAC population, we implemented systematic malnutrition screening in the Johns Hopkins pancreas multidisciplinary clinic (PMDC) and assessed the effectiveness of our nutrition referral system. METHODS: This was a single institution prospective study of patients seen in the PMDC, screened for malnutrition using the Malnutrition Screening Tool (MST) (score range=0 to 5, score > 2 indicates risk of malnutrition), and offered referrals to the oncology dietitian. Patients that requested a referral but did not attend a nutrition appointment were contacted by phone to assess barriers to seeing the dietitian. Univariate (UVA) and multivariable (MVA) analyses were carried out to identify predictors of referral status and appointment completion status. RESULTS: A total of 97 patients were included in the study, of which 72 (74.2%) requested a referral and 25 (25.8%) declined. Of the 72 patients who requested a referral, 31 (43.1%) attended an appointment with the oncology dietitian. Data on information session attendance was available for 35 patients, of which 8 (22.9%) attended a pre-clinic information session in which the importance of optimal nutrition was highlighted. On MVA, information session attendance was significantly associated with requesting a referral (OR: 11.1, 95% CI 1.12-1.0E3, p=0.037) and successfully meeting with the oncology dietitian (OR: 5.88, 95% CI 1.00-33.3, p=0.049). CONCLUSION: PMDC teams should institute educational initiatives on the importance of optimal nutrition in order to increase patient engagement with nutrition services.
Asunto(s)
Adenocarcinoma , Desnutrición , Neoplasias Pancreáticas , Humanos , Evaluación Nutricional , Estudios Prospectivos , Neoplasias Pancreáticas/terapia , Estado Nutricional , Desnutrición/diagnóstico , Desnutrición/etiología , Desnutrición/terapia , Derivación y Consulta , Neoplasias PancreáticasRESUMEN
We aimed to evaluate the impact of time from stereotactic body radiation therapy (SBRT) to surgery on treatment outcomes and post-operative complications in patients with borderline resectable or locally advanced pancreatic cancer (BRPC/LAPC). We conducted a single-institutional retrospective analysis of patients with BRPC/LAPC treated from 2016 to 2021 with neoadjuvant chemotherapy followed by SBRT and surgical resection. Covariates were stratified by time from SBRT to surgery. A Cox regression model was used to identify variables associated with survival outcomes. In 171 patients with BRPC/LAPC, the median time from SBRT to surgery was 6.4 (range: 2.7-25.3) weeks. Hence, patients were stratified by the timing of surgery: ≥6 and <6 weeks after SBRT. In univariable Cox regression, surgery ≥6 weeks was associated with improved local control (LC, HR 0.55, 95% CI 0.30-0.98; p = 0.042), pathologic node positivity, elevated baseline CA19-9, and inferior LC if of the male sex. In multivariable analysis, surgery ≥6 weeks (p = 0.013; HR 0.46, 95%CI 0.25-0.85), node positivity (p = 0.019; HR 2.09, 95% CI 1.13-3.88), and baseline elevated CA19-9 (p = 0.002; HR 2.73, 95% CI 1.44-5.18) remained independently associated with LC. Clavien-Dindo Grade ≥3B complications occurred in 4/63 (6.3%) vs. 5/99 (5.5%) patients undergoing surgery <6 weeks and ≥6 weeks after SBRT (p = 0.7). In summary, the timing of surgery ≥6 weeks after SBRT was associated with improved local control and low post-operative complication rates, irrespective of the surgical timing. Further investigation of the influence of surgical timing following radiotherapy is warranted.
RESUMEN
PURPOSE: Surgical resection is the only potential curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), but unfortunately most patients recur within 5 years of surgery. This article aims to assess the practice patterns across major academic institutions and develop consensus recommendations for postoperative imaging and interpretation in patients with PDAC. METHODS: The consensus recommendations for postoperative imaging surveillance following PDAC resection were developed using the Delphi method. Members of the Society of Abdominal Radiology (SAR) PDAC Disease Focused Panel (DFP) underwent three rounds of surveys followed by live webinar group discussions to develop consensus recommendations. RESULTS: Significant variations currently exist in the postoperative surveillance of PDAC, even among academic institutions. Differentiating common postoperative inflammatory and fibrotic changes from tumor recurrence remains a diagnostic challenge, and there is no reliable size threshold or growth rate of imaging findings that can provide differentiation. A new liver lesion or peritoneal nodule should be considered suspicious for tumor recurrence, and the imaging features should be interpreted in the appropriate clinical context (e.g., CA 19-9, clinical presentation, pathologic staging). CONCLUSION: Postoperative imaging following PDAC resection is challenging to interpret due to the presence of confounding postoperative inflammatory changes. A standardized reporting template for locoregional findings and report impression may improve communication of relaying risk of recurrence with referring providers, which merits validation in future studies.
Asunto(s)
Carcinoma Ductal Pancreático , Enfermedades Gastrointestinales , Neoplasias Pancreáticas , Radiología , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Tomografía Computarizada por Rayos X , Neoplasias PancreáticasRESUMEN
Background: Amongst patients with recurrent hepatocellular carcinoma (HCC) post-liver transplantation, systemic therapy options may be limited by immunosuppression or poor performance status. Thus, we aimed to assess the impact of metastasis-directed therapy to all sites of disease (MDT-All) in HCC patients with limited disease recurrence [i.e., oligorecurrence (oligoM1)] post-transplantation and characterize pre-transplant characteristics associated with oligoM1. Methods: In this retrospective cohort study, patients at a single institution with recurrent HCC post-liver transplantation were identified. OligoM1 disease was defined as ≤3 lesions at recurrence, while polyrecurrent (polyM1) disease was defined as >3 lesions. Outcomes were compared in patients with oligoM1 disease by receipt of MDT-All. Regression analyses were used to identify predictors of polyM1 disease and characteristics associated with post-recurrence outcomes. Results: Forty-three patients with recurrent HCC post-liver transplantation from 2005-2022 were identified. Twenty-seven (63%) patients had oligoM1. Microvascular invasion was independently associated with polyM1 [odds ratio (OR): 14.64; 95% confidence interval (CI): 1.48-144.77; P=0.022]. Elevated alpha-fetoprotein (AFP) ≥400 ng/mL [hazard ratio (HR): 2.44; 95% CI: 1.08, 5.52; P=0.033] at recurrence was independently associated with inferior overall survival (OS), while oligoM1 (HR: 0.42; 95% CI: 0.21, 0.87; P=0.018) was independently associated with favorable OS. Amongst patients with oligoM1 who received MDT-All (n=15) median OS was 38.4 vs. 16.1 months for those who did not receive MDT-All (log-rank P=0.021). There was a non-significant improvement in polyprogression-free survival (polyPFS) (median 14.0 vs. 10.7 months, P=0.1) amongst oligoM1 patients who received MDT-All compared to those who did not. Conclusions: Receipt of MDT-All was associated with improved OS amongst patients with limited HCC disease recurrence following liver transplantation.
RESUMEN
BACKGROUND AND PURPOSE: Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC. METHODS: Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P<0.05). RESULTS: A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P<0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045). CONCLUSIONS: For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.
Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Radiocirugia , Humanos , Neoplasias Pancreáticas/patología , Terapia Neoadyuvante , Carcinoma Ductal Pancreático/cirugía , Adenocarcinoma/patología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a "Triangle Volume" (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). METHODS: Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival. DISCUSSION: If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach. Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513.