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J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
J Surg Oncol. 2011 August 1; 104(2): 155–161. doi:10.1002/jso.21954.
Neoadjuvant GTX Chemotherapy and IMRT-Based
Chemoradiation for Borderline Resectable Pancreatic Cancer
Manish Patel, M.D., Sarah Hoffe, M.D., Mokenge Malafa, M.D., Pamela Hodul, M.D., Jason
Klapman, M.D., Barbara Centeno, M.D., Jongphil Kim, Ph.D., James Helm, M.D., Ph.D.,
Tiffany Valone, P.A., and Gregory Springett, M.D., Ph.D.
Division of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute,
Tampa, FL U.S.A
Abstract
Background and Objectives—To improve the likelihood of achieving a margin-free
resection, neoadjuvant induction chemotherapy with GTX (gemcitabine, docetaxel, and
capecitabine) followed by 5-FU-IMRT was administered to patients with borderline resectablepancreatic cancer. The utility of CT, EUS, PET, and CA 19-9 during diagnostic workup andassessment of response was also examined.
Methods—Seventeen patients with borderline resectable pancreatic cancer received a median of
3 cycles of neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT with dose
painting. CA 19-9, CT mass size, and PET SUV were examined before and after neoadjuvant
treatment.
Results—Diagnostic EUS and CT scans displayed similar mean mass sizes and extent of
vascular involvement. Eight of the 17 patients achieved an R0 resection. Median CA 19-9 levels,
CT mass size, and PET SUV all significantly decreased after neoadjuvant therapy. The median
progression-free survival and overall survival were 10.48 months and 15.64 months respectively.
Six patients are still alive.
Conclusions—Neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT shows
promise in improving the likelihood of resectability with negative margins in borderline resectable
pancreatic cancer. CT and EUS play complimentary roles during diagnostic workup. CT scans,
CA 19-9, and PET scans are useful in judging response to neoadjuvant therapy.
Keywords
chemotherapy; borderline resectable; pancreatic cancer; GTX; neoadjuvant Introduction
Long-term survival after a diagnosis of pancreatic cancer is best achieved in patients whoare able to undergo a pancreaticoduodenectomy (Whipple procedure) with negative marginsand who are diagnosed prior to the development of distant metastases. Unfortunately, only20% of pancreatic cancer patients have resectable disease at presentation [1]. The medianoverall survival of patients who undergo complete resection with negative margins rangesbetween 12 and 26 months [2].
Correspondence: Gregory Springett, M.D., Ph.D., H. Lee Moffitt Cancer Center & Research Institute, SRB-3, Rm 23009, 12902Magnolia Drive, Tampa, Florida, 33612, Phone: 813-745-6898, Fax: 813-745-8332, manish.patel@moffitt.org.
Approximately 40% of patients with pancreatic cancer present with locally advanced diseasethat is not amenable to surgical resection [3]. One-third of these patients will be marginally or “borderline resectable.” Numerous retrospective studies have demonstrated an associationof positive margins with higher local failure rates and poorer overall and disease-freesurvivals for patients with borderline resectable pancreatic cancer [4–6]. Attempting aresection upfront for this disease is associated with a higher probability of necessitatingvascular reconstruction and obtaining positive margins. The application of multimodalityneoadjuvant therapies can have the greatest impact on borderline resectable pancreaticcancer by increasing the likelihood of obtaining negative margins at the time of resectionand yielding survival comparable to that achieved by upfront resectable disease.
To our knowledge, a completed study reporting clinical outcomes for one particularneoadjuvant regimen for borderline resectable pancreatic cancer has never been published.
Numerous clinical trials have taken place with different multiagent neoadjuvantchemotherapeutic regimens with radiation for locally advanced pancreatic cancer, including5-FU, gemcitabine, cisplatin, mitomycin, paclitaxel, and streptozotocin [7–11]. Percentresectability has ranged between 9% and 32% among the trials. Evaluating the literature inthis setting is complicated by combining borderline resectable patients with those patientswho actually have locally advanced unresectable disease.
It is hypothesized that a period of induction chemotherapy might allow for the selection ofthose locally advanced patients who might truly benefit from subsequent chemoradiation. Ina retrospective analysis conducted by Krishnan et al [12], median overall survival wassuperior in the patients who received induction chemotherapy with a gemcitabine basedregimen compared to the chemoradiation alone group (11.9 vs. 8.5 mo). Fogelman et al firstreported the use of GTX consisting of gemcitabine, docetaxel, and capecitabine as inductionchemotherapy followed by gemcitabine-based chemoradiation [13]. The abstract described aseries of 14 patients with locally advanced pancreatic cancer who received the GTXinduction regimen. Eight patients (57%) were downstaged to resectability with negativemargins. GTX was developed based on the demonstration of preclinical in vitro synergy ofthe combination. In the metastatic setting, GTX chemotherapy has shown a response ratethat approaches 30–40% with a median survival of 11.2 months [14].
In the past, the determination of whether pancreatic cancer was resectable, borderlineresectable, or unresectable was made at surgical exploration. The development of modernimaging techniques with improved resolution has allowed for the preoperative staging ofpatients. Computed Tomography (CT), Endoscopic Ultrasound (EUS), and PositronEmission Tomography (PET) scans are available imaging options that can be used during the diagnostic workup and management of pancreatic cancer. These modalities can offervaluable information during the management of borderline pancreatic cancer, however acomparison of their utility has not been formally performed.
Given the lack of completed prospective studies specifically involving borderline resectablepancreatic cancer, we have performed a retrospective analysis of our institution’s experiencewith neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT for this disease.
An ECOG prospective trial (E1200) for borderline resectable disease was recently publisheddescribing tolerability and resectability after a particular neoadjuvant regimen, however thetrial was not completed as it closed early due to poor accrual [15]. The utility of ourparticular regimen for borderline resectable pancreatic cancer has not been formallypublished elsewhere. The main objective was to determine if GTX induction chemotherapyfollowed by 5-FU-IMRT optimizes the likelihood of achieving a margin-free resection.
Comparisons were made between the findings of CT, EUS, PET, and CA 19-9 to offerinsight into their utility during diagnostic workup and treatment. To our knowledge, this J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
particular analysis has not formally been performed specifically for borderline resectablepancreatic cancer.
Materials and Methods
Patient Population
Clinical data on 18 borderline resectable pancreatic cancer patients between February 2006and February 2009 treated at the Moffitt Cancer Center and Research Institute wereretrieved from a database maintained by the GI Pancreatic Tumor Program. None of the 18patients were exposed to previous chemotherapy or radiation to the pancreas. Approximately250 new cases of pancreatic cancer are seen per year at Moffitt. Approximately 30 patientsper year were likely borderline resectable during the timeframe of the retrospective study.
The number of patients that now receive neoadjuvant therapy at our institution hassignificantly increased based on the results of this study. Prior to initiating treatment, allpatients had leukocyte counts >3000/uL, ANC ≥1000/uL, Creatinine clearance ≥ 60 mL/min/1.73m2, T Bilirubin ≤ULN, and AST and ALT ≤ 2.5 × ULN. Performance status wasrecorded using the Eastern Cooperative Oncology Group (ECOG) scale [16].
H. Lee Moffitt Cancer Center Diagnostic Algorithm for Borderline Resectable Pancreatic
Cancer
A baseline evaluation of all patients consisted of a detailed history and physicalexamination, complete blood count, blood chemistries, and CA 19-9 level. At MoffittCancer Center, we attempt to obtain an initial EUS, a thin cut pancreatic protocol CT, andPET scan for all patients with possible borderline resectable disease. PET scanning as amodality for the diagnosis, staging, and monitoring of treatment of pancreatic cancer andother cancers is currently being assessed nationally in a Medicare outcomes study. Ourcenter is a participant in the National Oncologic PET Registry, which provides us theopportunity to evaluate this imaging modality in pancreatic cancer. Data from our institutionreported by Farma et al [17] has shown that in patients with potentially resectable pancreaticcancer, PET/CT imaging can change management in 11% of patients. After the initialassessment, patients were reviewed by our GI Tumor Board and an agreement for thediagnosis of borderline resectable pancreatic cancer was made for each patient.
For this retrospective study, mass sizes and vessel involvement displayed by the diagnosticCT and EUS studies were retrieved. The diagnosis of borderline resectable pancreatic cancerwas mainly made by CT or EUS. Three of the 18 patients were found to be borderlineresectable during an initial surgical resection attempt based on a CT or EUS diagnosis ofresectable pancreatic cancer. A successful tissue diagnosis was made from a biopsy using EUS in 14 patients and by using CT guidance in 4 patients. If a patient had an EUS or CTthat displayed evidence of locally advanced pancreatic cancer that was not consistent withborderline resectable disease, he or she was not included in the database.
The H. Lee Moffitt Cancer Center utilizes specific criteria for the classification of borderlineresectable pancreatic cancer, which encompasses definitions used elsewhere [18,19].
Borderline resectable patients were those who had circumferential tumor abutment with thesuperior mesenteric vein (SMV), portal vein (PV), or superior mesenteric artery (SMA)≤180°. Short segment (approximately 1.5 cm) encasement of the PV or SMV that wasamenable to partial vein resection and reconstruction was also classified as borderline.
Patients who had encasement of the gastroduodenal artery up to the origin of the hepaticartery were also considered borderline resectable. Involvement of both the PV/SMV andSMA that would require resection and reconstruction of both arterial and venous systemswas classified as unresectable. Patients who had encasement of the superior mesenteric J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
artery (SMA), celiac artery, aorta, or inferior vena cava (IVC) were classified asunresectable.
Neoadjuvant Treatment
All of the borderline resectable pancreatic cancer patients received induction chemotherapywith GTX. Gemcitabine (Eli Lilly) was given at 750mg/m2 on Days 4 and 11. Docetaxel(Sanofi Aventis) was administered at 30mg/m2 on Days 4 and 11. Capecitabine (Genentech)was given at 750mg/m2 BID on Days 1–14. This cycle was repeated every 21 days, as usedin the original metastatic study involving GTX [14].
One week after completing induction GTX chemotherapy, the patients began concurrentchemoradiation with 5-FU (continuous infusion, 225mg/m2) and Intensity-ModulatedRadiation Therapy (IMRT). With IMRT, radiation oncologists are able to deliver the sameor higher doses to the target while sparing more normal tissue. IMRT was administered withdose painting in the majority of cases, with the intent to deliver a higher dose each fractionto gross disease and a lower dose each fraction to the microscopic disease at highest risk.
All cases in this series were planned by the same GI radiation oncologist. 4D CT simulationwas performed with the patient in the supine position using immobilization with thepatient’s arms over their head. An initial scan using IV and oral contrast was performed in free breathing unless there was a contraindication such as a high creatinine or a contrastallergy. Neither abdominal compression nor respiratory gating techniques were utilizedsince the patient was receiving a 5 week course of therapy. Two target volumes were drawn.
The first was the GITV, the gross internal target volume, taking into account the primarydisease in all phases of respiration. A second was a subjective CITV, the clinical internaltarget volume, reflecting the microscopic sites of highest risk. No attempt was made to coverall potential sites of nodal risk. Since image guidance was not utilized for the treatment, amargin of 1cm was placed around the GITV and the CITV for the creation of the respectivePTV 50 and PTV 45. The intent of treatment was thus to irradiate the gross disease target at200cGy per fraction for 25 fractions while delivering a lower dose of 180cGy per fraction tothe microscopic clinical volume felt to be at highest risk.
After induction chemotherapy and chemoradiation, the patients were restaged. CT and PETscans were performed approximately 4 weeks after completing chemoradiation. A CA 19-9level was drawn at this time as well. The changes in CA 19-9, CT mass size, and PET SUVwere calculated using the values obtained prior to and after neoadjuvant therapy.
Surgical Assessment
After completing neoadjuvant treatment and reviewing the data, all potentially resectablepatients were discussed by our GI Tumor Board. A consensus was made on the potential forresectability based on standard NCCN radiologic guidelines, including a lack of distantmetastases, tumor thrombus, or vascular abutment. For those patients who underwentsurgery and had a resection, the operating surgeon and pathologist determined if an R0 orR1 resection was achieved. The operation was defined as an R0 resection if there was nomicroscopic tumor found at the margin and as an R1 resection if a margin wasmicroscopically positive. Pancreaticoduodenectomy was performed in the standard fashion.
Segmental resection of the SMA, PV, or SMV/PV confluence was performed when theoperating surgeon could not separate the pancreatic head from these vessels without leavingtumor on the vessel.
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Follow-up and Statistical Analyses
The patients were seen in clinic approximately 1 month after surgery and then every 3–4 months thereafter. The visits included a complete physical examination, complete bloodcount, and blood chemistries. Ordering CA 19-9 levels and CT scans were done in thesurveillance time period, but not in fixed intervals. Overall survival was calculated from theinitiation date of neoadjuvant therapy until the date of death or last contact. Progression freesurvival was calculated from the initiation date of neoadjuvant therapy until the last date atwhich the patient was known to be free of disease. Overall survival and progression-freesurvival curves were created by the Kaplan Meier method [20]. Median follow-up time forthe patients who are still alive was calculated from the initiation of neoadjuvant therapy untilthe last follow-up visit.
Agreement between CT and EUS mass size was assessed by the Concordance CorrelationCoefficient. Agreement of vascular involvement between CT and EUS was assessed by akappa index. Correlation between CT mass size and CA 19-9/PET SUV was analyzed bycalculating Pearson correlation coefficients. Statistical differences between pre and post-neoadjuvant CA 19-9 levels, PET SUV, and CT mass sizes were assessed using theWilcoxon signed-rank test. The SPSS software version 15.0 was used for all statisticalanalyses.
Patient Characteristics
As displayed in Table I, the median age at diagnosis was 67 with a range from 45–82 for the18 patients involved in this retrospective analysis. All patients began with an ECOGPerformance Status ≤ 1 prior to starting therapy. Twelve of the patients were male and 6were female. Seventy-two percent of the masses (n=13) involved the pancreatic head, 11.1%(n=2) were located in the body, and 16.7% (n=3) involved the body/tail. A pretreatment CTwas performed in all 18 patients, while 14 of the patients underwent an EUS as well. Meanmass size by CT was 3.4 cm (n=17) and 3.3 cm by EUS (n=14). The median number ofadministered cycles of GTX was 3 in our retrospective analysis. Thirteen patients received 3cycles, one was given 4 cycles, and four received 2 cycles. Median time from the date ofdiagnosis to start of chemotherapy was 18 days. The median IMRT dose was 5000cGy.
Thirteen patients received 5000cGy, three were given 4500cGy, and one received 5200cGy.
One patient did not receive IMRT because of disease progression while receiving inductionchemotherapy, thus only 17 patients finished the complete neoadjuvant regimen.
Sites of vascular abutment that defined the diagnosis of borderline resectable disease are illustrated in Table II. Abutment could be assessed in 15 of the 18 patients by CT and in 10of the 14 patients who had an EUS. The majority of the borderline resectable cases consistedof portal vein (PV) and superior mesenteric vein (SMV) abutment. Utilizing CT, 22% of thecases displayed abutment with the PV, 28% with the SMV, and 17% with the PV/SMVconfluence. EUS suggested that 29% of the cases had abutment with the PV, 21% with theSMV, and 14% with the PV/SMV confluence. Three patients were not found to have vesselabutment by the initial CT and EUS, but abutment was seen when taken for immediateresection. Surgery was aborted in these 3 cases and they were then diagnosed as havingborderline resectable disease.
Pretreatment CA19-9 levels and PET SUV are displayed in Table III. The median CA 19-9level (n=18) prior to treatment was 483. The median pretreatment max SUV for the 15patients who had a PET scan was 5.7.
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Response to Neoadjuvant Therapy
CA 19-9, CT mass size, and PET SUV significantly decreased after neoadjuvant therapy (Table III). Sixteen patients had both pre and post-therapy CA 19-9 levels checked. MedianCA 19-9 decreased from 483 to 50 (p<0.01), representing a median 83% decrease. Eight outof the 16 patients had a >85% decrease in CA 19-9 levels. Fourteen patients had both preand post-therapy PET scans. Median PET max SUV decreased from 5.7 to 1.6 (p<0.001).
Seven of the 14 patients (50%) had a 100% decrease in PET SUV. Graphical representationsof the significant change in CA 19-9 levels and PET SUV after neoadjuvant therapy areillustrated in Figure 1 and 2 for each patient who had pre and post CA 19-9 levels and PETscans. Median CT mass size decreased from 3.35 to 2.70cm after neoadjuvant therapy(p=0.002).
Table IV displays the surgical outcomes after neoadjuvant therapy. Seventeen out of the 18patients from the database finished neoadjuvant therapy. One patient progressed whilereceiving induction chemotherapy, so neoadjuvant therapy was not completed. Following adiscussion at our GI Tumor Board, 14 out of the 17 patients (82%) who completedneoadjuvant therapy met radiologic evidence for resectability based on NCCN guidelinesand were subsequently brought to surgery. Of these 14 patients who went to surgery,pancreatic mass resections were performed in 9 cases (64%). Two of the cases involvedreconstruction of the PV/SMV. Pancreatic disease could not be resected in 5 patients at exploration due to unexpected encasement of the SMA/SMV in 2 cases, encasement of theSMA/SMV/PV in 1 case, mesenteric disease and SMV encasement in 1 case, and peritonealmetastases in another case that were not found on the post-neoadjuvant scans. From the 9patients who were able to undergo resections, an R0 resection was achieved in 8 of thesecases (89%). Overall, 8 out of the 17 patients (47%) who finished our neoadjuvant protocolachieved an R0 resection. By ITT analysis, 8 of 18 borderline resectable patients underwenta successful Whipple procedure with negative margins. The common bile duct, proximalgastric, pancreatic, retroperitoneal, and duodenal margins were examined for each resection.
Of the 8 R0 resection specimens, the pathologist noted that 7 displayed minimally residualdisease that was consistent with significant treatment effect. The other specimen did notreveal any carcinoma and was completely fibrotic. The median time from the initiation ofneoadjuvant therapy to the date of surgery was 5.82 months.
Survival analysis is not complete as 6 out of the 18 patients are still alive. Three of these 6patients are without evidence of disease. Of the initial 18 patients, one patient progressed todevelop liver metastases during induction chemotherapy and could not finish neoadjuvanttherapy. Nine other patients progressed after neoadjuvant therapy. However, only 3 of thesepatients progressed after resection. Progression involved development of liver metastases (n=1), peritoneal metastases (n=1), lung metastases (n=2), malignant ascites/growth oftumor (n=1), increased lymphadenopathy/growth of tumor (n=1), vascular encasement(n=1), and significantly worsening CA 19-9 levels/symptoms (n=2). Kaplan-Meier curvesfor progression-free survival and overall survival are illustrated in Figure 3. Medianprogression-free survival was 10.48 months (95% CI: 6.01–14.55) and median overallsurvival was 15.64 months (95% CI: 14.49–23.92); however, 6 patients are still alive.
Median follow-up time for the 6 patients who are still alive was 13.27 months.
Toxicities and Complications
The toxicities related to neoadjuvant therapy did not prevent any of the patients fromcompleting treatment or cause any subsequent surgical morbidity. Significant temporarytoxicities related to treatment consisted of hand-foot syndrome (n=7), mucositis (n=8),abdominal pain (n=1), diarrhea (n=3), febrile neutropenia (n=1), and thrombocytopenia(n=3). Post-operative complications included a pulmonary embolism (n=1), wound infection J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
(n=1), seizures (n=1), and acute renal failure (n=1). There were no deaths from neoadjuvanttherapy or surgery. All patients who were admitted for surgery were discharged home.
Correlation between Diagnostic Modalities
The mean mass size determined by CT did not differ when compared to that measured byEUS. Primary tumor size as measured by EUS was significantly correlated with the sizemeasured by CT scan. The Concordance correlation coefficient was 0.85 for patients whohad both CT and EUS (n=13, 95% CI: 0.596–0.950), consistent with statistical agreement.
As shown in Table V, CT and EUS agreed upon the extent of vascular involvement in 12 outof the 14 patients (86%) who had both pretreatment CT and EUS assessments (p=0.02 Chi-square test). Statistical reproducibility was demonstrated by a Kappa index of 0.59 (95% CI:0.1–1.0).
When investigating for a possible association between CA 19-9 and CT mass size, thePearson correlation coefficient (r) was found to be −0.084. Therefore, CA19-9 was notcorrelated with tumor size as measured by CT scan (p = 0.75). Less than 1% of thevariability in CA19-9 could be explained by the variability in size by CT scan as indicatedby r2 = 0.0071.
When evaluating for a possible association between PET SUV and CT mass size, the Pearson correlation coefficient (r) was found to be 0.38. Thus, SUV max was notsignificantly correlated with tumor size as measured by CT scan (p = 0.18). Only 15% of thevariability in SUV max could be explained by the variability in size by CT scan as indicatedby r2 = 0.1475.
Discussion
The current retrospective analysis displays promising outcomes for a particular neoadjuvantregimen specifically in borderline resectable pancreatic cancer. Completed prospectivestudies specifically involving only borderline resectable disease do not exist. It is known thatlong-term survival after a diagnosis of pancreatic cancer is best achieved in patients who arediagnosed prior to the development of metastases and who are able to undergo a Whippleprocedure with negative margins. Multimodality neoadjuvant therapies can have the greatestimpact on borderline resectable pancreatic cancer patients by increasing the likelihood ofobtaining an R0 resection, as shown in a meta-analysis specifically examining neoadjuvanttherapy for pancreatic cancer [21]. Induction chemotherapy followed by chemoradiation hasled to efficacious results in locally advanced unresectable pancreatic cancer [12,13]. Thefact that most successfully resected patients display recurrence provides evidence that micrometastases are likely to present at an early stage of the disease. Inductionchemotherapy not only offers the advantage of eradicating micrometastatic disease, but itcan also theoretically decrease tumor size allowing better response to subsequentchemoradiation and serve as a screening test for response to the chosen chemotherapeuticagents.
Our analysis demonstrates that neoadjuvant GTX induction chemotherapy followed by 5-FUIMRT has significant activity in borderline resectable pancreatic cancer while satisfying thegoal of achieving clinical outcomes comparable to upfront resectable disease. Median CA19-9 levels, CT mass size, and PET SUV all significantly decreased after neoadjuvanttherapy. The data illustrate that all three modalities, CA 19-9, CT scans, and PET scansallow the opportunity to judge response to neoadjuvant therapy. Overall, 8 out of the 17patients who finished our neoadjuvant regimen achieved a successful Whipple procedurewith negative margins. These surgical outcomes compare favorably with historical data [7–11,13,22–24] that utilized various neoadjuvant regimens to yield resections for locally J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
advanced disease with negative margins. In addition, only 2 patients needed vascularreconstruction after neoadjuvant therapy. Based on historical data, the percentage of patients necessitating vascular reconstruction would be expected to be much higher if taken forresection upfront. Our analysis yielded a progression-free survival of 10.48 months and amedian overall survival of 15.64 months. Six out of the 18 patients are still alive. It isevident that neoadjuvant GTX induction chemotherapy followed by chemoradiation canachieve the goal of an R0 resection in borderline resectable pancreatic cancer and can lead tosurvival that is similar to what has been found for resectable pancreatic cancer at diagnosis[2]. This neoadjuvant regimen also involves minimal toxicity with a convenient dosingschedule.
The retrospective analysis also facilitated an assessment of the utility of CA 19-9, CT scans,and PET scans in the diagnosis and management of borderline resectable disease that has notformally been published in the past. The mean mass size and extent of vascular abutmentdetermined by CT did not differ when compared to EUS, which suggests that CT and EUScan play complimentary roles during diagnostic workup. In terms of these diagnostic tools,the study was important as it did not illustrate statistical associations between CT mass sizeand PET SUV and between CA 19-9 levels and CT mass size. Although known to be quitehelpful in the majority of the cases, CT and PET scans failed to identify occult disease in 5patients after neoadjuvant therapy. These 5 patients were brought to the operating room, but their disease could not be resected due to gross visual evidence of occult disease.
Major strengths and weaknesses are evident when examining the current study. Theretrospective analysis mostly consisted of patients that were treated by a dedicated multi-disciplinary team at a single institution. A multidisciplinary approach allows uniformity inobtaining tissue diagnoses, accurate radiologic interpretation, adherence to the definition ofresectability, consistent treatment approaches, and standardized follow-up assessments. Thestudy is only made up of borderline resectable pancreatic cancer that allows the opportunityto closely examine the various diagnostic modalities and treatment effects on this particulardisease. Neoadjuvant therapy was completed in 17 out of 18 patients, which allows accurateassessment for the ability to obtain an R0 resection with the particular regimen. The studyalso allowed an opportunity to examine the utility of CT, PET, and CA 19-9 duringdiagnosis and during the assessment of response. The main weakness of the analysis wasthat it was retrospective, although the patients were treated in a uniform fashion. The smallsample size involved in the imaging and CA 19-9 comparisons, as well as in assessingsurgical response to neoadjuvant therapy, also represents a limitation. However, studiesinvolving large sample sizes do not exist for the borderline resectable pancreatic cancerpopulation.
In summary, we report an effective neoadjuvant regimen for borderline resectable pancreaticcancer that can lead to increasing the likelihood of R0 resections. This analysis provides thefirst published data displaying the response of borderline resectable disease to GTXinduction chemotherapy followed by 5-FU IMRT. GTX chemotherapy displays activity inborderline resectable disease based on our results. The neoadjuvant regimen proved to bewell tolerated and did not pose difficulties in administration or scheduling. The resultsobtained by utilizing this regimen are favorable to historical data and will need to beexplored further. Our group hopes to perform a prospective study to accomplish thisobjective. We will also explore novel radiotherapy approaches, such as incorporatingStereotactic Body Radiotherapy (SBRT).
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Acknowledgments
Dr Springett receives grant support from the Robert Wood Johnson Foundation, Amos Faculty Development References
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2006; 24(7):1145–1151. [PubMed: 16505434] J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Figure 1.
Percent change in CA 19-9 level after neoadjuvant therapy for each of the 16 patients who
had pre and post CA 19-9 levels drawn. Eight patients had >85% decrease in their CA 19-9
levels.
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Figure 2.
Percent change in PET SUV after neoadjuvant therapy for each of the 14 patients who had
pre and post PET scans performed. Seven patients had a complete loss of PET avidity.
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Figure 3.
Kaplan-Meier curves for progression-free survival and overall survival for the 18 borderline
resectable pancreatic cancer patients. Median OS was 15.64 mo and the median PFS was
10.48 mo. Six patients are still alive (censored).
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Characteristics of the 18 Borderline Resectable Pancreatic Cancer Patients *mean mass size by CT did not differ when compared to EUS for those patients who had both studies (p=0.52, n=13); Concordance correlationcoefficient of r=0.85 J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Three patients were not found to have vessel abutment by initial CT or EUS, but abutment was seen when taken for immediate resection; PV =portal vein; SMA = superior mesenteric artery; SMV = superior mesenteric vein J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Table III
Biochemical and Imaging Characteristics before and after Neoadjuvant Therapy Pre-GTX/IMRT
Post-GTX/IMRT
*8/16 patients had a > 85% decrease in CA 19-9 levels #7/14 patients had a 100% decrease in PET SUV max J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Surgical Outcomes for Patients who Finished Neoadjuvant Therapy Percent Resected from those who had Surgery Percent R0 Resections from those who finished Therapy *One out of the 18 patients progressed while receiving induction chemotherapy and did not finish neoadjuvant therapy J Surg Oncol. Author manuscript; available in PMC 2012 August 01.
Vessel Abutment Agreement by CT and EUS for Patients who had Both Studies Vessel Abutment by CT
Vessel Abutment by EUS
J Surg Oncol. Author manuscript; available in PMC 2012 August 01.

Source: http://surgonc.org/docs/default-source/fellows-articles-july/gtx-imrt-br-panc.pdf?sfvrsn=2