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Optimizing neoadjuvant radiotherapy for resectable and borderline resectable pancreatic cancer using protons

World Journal of Gastrointestinal Surgery 2019年第7期11卷 303-307页

作者： Romaine Charles Nichols michael rutenberg Department of Radiation Oncology University of Florida College of Medicine

Approximately 25%of patients diagnosed with pancreatic cancer present with non-metastatic resectable or borderline resectable ***,the cure rate for these“curable”patients is only in the range of 20%.Local-regional failure rates may exceed 50%after margin-negative,node-negative pancreatectomy,but up to 80%of resections are associated with regional lymph node or margin *** systemic drug therapy and chemotherapy may prevent or delay the appearance of distant metastases,it is unlikely to have a significant impact on local-regional disease *** radiotherapy would represent a rational intervention to improve local-regional *** barrier to preoperative radiotherapy is the concern that it could potentially complicate what is already a long and complicated *** the radiotherapy is delivered with X-rays(photons),the entire cylinder of the abdomen is irradiated;therefore,an operating surgeon may be reluctant to accept the associated risk of increased *** preoperative radiotherapy is delivered with protons,however,significant bowel and gastric tissue-sparing is achieved and clinical outcomes indicate that proton therapy does not increase the risk of operative complications nor extend the length of the procedure.

关键词： Radiation oncology Pancreatic cancer Proton therapy

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Proton therapy for pancreatic cancer

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World Journal of Gastrointestinal Oncology 2015年第9期7卷 141-147页

作者： Romaine C Nichols Soon Huh Zuofeng Li michael rutenberg Department of Radiation Oncology University of Florida

Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.

关键词： Proton therapy Pancreatic cancer Review

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Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer

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World Journal of Gastrointestinal Surgery 2017年第4期9卷 103-108页

作者： Kathryn E Hitchcock R Charles Nichols Christopher G Morris Debashish Bose Steven J Hughes John A Stauffer Scott A Celinski Elizabeth A Johnson Robert A Zaiden Nancy P Mendenhall michael S rutenberg Department of Radiation Oncology University of Florida Department of Surgical Oncology UF Health Cancer Center-Orlando Health Department of Surgery University of Florida Department of Surgery Mayo Clinic Department of Surgery Baylor University Medical Center at Dallas Department of Hematology/Oncology Mayo Clinic Department of Hematology/Oncology Baptist Health

AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic *** From April 2010 to September 2013,15 patients with initially unresectable pancreatic cancer were treated withproton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy(RBE) to the gross disease and 1 patient received 50.40 Gy(RBE) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration,of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included:Laparoscopic standard pancreaticoduodenectomy(n = 3),open pyloris-sparing pancreaticoduodenectomy(n = 1),and open distal pancreatectomy with irreversible electroporation(IRE) of a pancreatic head mass(n = 1). RESULTS The median patient age was 60 years(range,51-67). The median duration of surgery was 419 min(range,290-484),with a median estimated blood loss of 850 cm^3(range,300-2000),median ICU stay of 1 d(range,0-2),and median hospital stay of 10 d(range,5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection(n = 1),delayed gastric emptying(n = 1),and ischemic gastritis(n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient,after negative pancreatic head biopsies,underwent IRE followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo(range,10-30).CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after

关键词： Pancreatic cancer Pancreatectomy Pancreas Proton therapy Radiotherapy

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Targeting KRAS in pancreatic adenocarcinoma:Progress in demystifying the holy grail

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World Journal of Clinical Oncology 2023年第8期14卷 285-296页

作者： Ahmed Elhariri Ahmed Alhaj Daniel Ahn Mohamad Bassam Sonbol Tanios Bekaii-Saab Christina Wu michael Scott rutenberg John Stauffer Jason Starr Umair Majeed Jeremy Jones Mitesh Borad Hani Babiker Division of Hematology-Oncology Department of MedicineMayo Clinic FloridaMayo Clinic Cancer CenterJacksonvilleFL 32224United States Division of Hematology-Oncology Department of MedicineMayo Clinic ArizonaMayo Clinic Cancer CenterPhoenixAZ 85054United States Department of Radiation-Oncology Mayo Clinic FloridaMayo Clinic Cancer CenterJacksonvilleFL 32224United States Department of Surgical Oncology Hepatopancreatobiliary SurgeryMayo Clinic FloridaJacksonvilleFL 32224United States

Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted *** extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.

关键词： Kirsten rat sarcoma virus Targeted therapy Pancreatic cancer Drug resistance Next generation sequencing Clustered regularly interspaced short palindromic repeats

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