Michael D. Chuong

Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated.

PURPOSEnStereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity.nnnMETHODS AND MATERIALSnA single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS).nnnRESULTSnSeventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%).nnnCONCLUSIONSnSBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.

Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma

Abstract Purpose. Limited data are available to guide neoadjuvant treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. Material and methods. We updated our institutional outcomes with a neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) approach. An IRB-approved analysis was performed of all BRPC and LAPC patients treated with our departmental treatment protocol. After staging, medically fit patients underwent chemotherapy for 2–3 months, with regimen at the discretion of the treating medical oncologist. Patients then received SBRT delivered in five consecutive daily fractions with median total radiation doses of 30 Gy to tumor and 40 Gy dose painted to tumor-vessel interfaces. This was followed by restaging imaging for possible resection. Overall survival (OS), event free survival (EFS), and locoregional control (LRC) rates were estimated and compared by Kaplan-Meier and log-rank methods. Results. We identified 159 patients, 110 BRPC and 49 LAPC, with 14.0 months median overall follow-up. The resection and margin negative (R0) rate for BRPC patients who completed neoadjuvant therapy was 51% and 96%, respectively. Estimated median OS was 19.2 months for BRPC patients and 15.0 months for LAPC patients (p = 0.402). Median OS was 34.2 months for surgically resected patients versus 14.0 months for unresected patients (p < 0.001). Five of 21 (24%) LAPC patients receiving FOLFIRINOX chemotherapy underwent R0 resection. In LAPC, FOLFIRINOX recipients underwent R0 resection more often than other chemotherapy recipients (5 of 21 vs. 0 of 28, p = 0.011). There was a trend for improved survival in those resected LAPC patients (p = 0.09). For those not undergoing resection, one year LRC was 78%. Any grade ≥ 3 potentially radiation-related toxicity rate was 7%. Conclusions. These data underscore the feasibility, safety, and effectiveness of neoadjuvant SBRT and chemotherapy for BRPC and LAPC.

Radiation Therapy and Esophageal Cancer

BACKGROUNDnSquamous cell carcinoma and adenocarcinoma account for more than 90% of all esophageal cancer cases. Although the incidence of squamous cell carcinoma has declined, the incidence of adenocarcinoma has risen due to increases in obesity and gastroesophageal reflux disease.nnnMETHODSnThe authors examine the role of radiation therapy alone (external beam and brachytherapy) for the management of esophageal cancer or combined with other modalities. The impact on staging and appropriate stratification of patients referred for curative vs palliative intent with modalities is reviewed. The authors also explore the role of emerging radiation technologies.nnnRESULTSnCurrent data show that neoadjuvant chemoradiotherapy followed by surgical resection is the accepted standard of care, with 3-year overall survival rates ranging from 30% to 60%. The benefit of adjuvant radiation therapy is limited to patients with node-positive cancer. The survival benefit of surgical resection after chemoradiotherapy remains controversial. External beam radiation therapy alone results in few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. Brachytherapy can provide better long-term palliation of dysphagia than metal stent placement. Although three-dimensional conformal treatment planning is the accepted standard, the roles of IMRT and proton therapy are evolving and potentially reduce adverse events due to better sparing of normal tissue.nnnCONCLUSIONSnFuture directions will evaluate the benefit of induction chemotherapy followed by chemoradiotherapy, the role of surgery in locally advanced disease, and the identification of responders prior to treatment based on microarray analysis.

Increased survival associated with surgery and radiation therapy in metastatic gastric cancer: a Surveillance, Epidemiology, and End Results database analysis.

Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients stratified by surgery and radiation therapy.

Lymph Node Harvest in Esophageal Cancer After Neoadjuvant Chemoradiotherapy

BackgroundThis study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT).MethodsAn analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model.ResultsWe identified 358 patients with a mean follow-up of 27.3xa0months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6xa0months and 52.7xa0%, 29.7xa0months and 30.4xa0%, and 17.7xa0months and 25.4xa0% (pxa0=xa00.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS.ConclusionsThe number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.

Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer

BACKGROUNDnNeoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) are utilized to increase margin negative (R0) resection rates in borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) patients. Concerns persist that these neoadjuvant therapies may worsen perioperative morbidities and mortality.nnnMETHODSnUpfront resection patients (n=241) underwent resection without neoadjuvant treatment for resectable disease. They were compared to BRPC or LAPC patients (n=61) who underwent resection after chemotherapy and 5 fraction SBRT. Group comparisons were performed by Mann-Whitney U or Fishers exact test. Overall Survival (OS) was estimated by Kaplan-Meier and compared by log-rank methods.nnnRESULTSnIn the neoadjuvant therapy group, there was significantly higher T classification, N classification, and vascular resection/repair rate. Surgical positive margin rate was lower after neoadjuvant therapy (3.3% vs. 16.2%, P=0.006). Post-operative morbidities (39.3% vs. 31.1%, P=0.226) and 90-day mortality (2% vs. 4%, P=0.693) were similar between the groups. Median OS was 33.5 months in the neoadjuvant therapy group compared to 23.1 months in upfront resection patients who received adjuvant treatment (P=0.057).nnnCONCLUSIONSnPatients with BRPC or LAPC and sufficient response to neoadjuvant multi-agent chemotherapy and SBRT have similar or improved peri-operative and long-term survival outcomes compared to upfront resection patients.

Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer.

BACKGROUNDnWhile clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described.nnnMETHODSnThis single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score.nnnRESULTSnWe evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS.nnnCONCLUSIONSnThese data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

Induction gemcitabine-based chemotherapy and neoadjuvant stereotactic body radiation therapy achieve high margin-negative resection rates for borderline resectable pancreatic cancer

ObjectivesPatients with borderline resectable pancreatic cancer (BRPC) have a higher probability of undergoing margin-negative resection after completing neoadjuvant therapy. Here, we describe a novel neoadjuvant approach using induction chemotherapy followed by stereotactic body radiation therapy (SBRT) for patients with BRPC.MethodsThis analysis included patients with nonmetastatic BRPC treated with neoadjuvant gemcitabine-based chemotherapy and five-fraction SBRT. Chemotherapy consisted of 3xa0cycles of Gemzar, Taxotere, and Xeloda. Patients were restaged to determine resectability, and nonmetastatic resectable patients underwent surgical resection.ResultsThirty patients completed neoadjuvant treatment and were offered surgical exploration. Seventeen patients (56.7xa0%) reported no acute adverse effects during SBRT. No grade 3 or higher toxicity was observed from SBRT. Twenty-nine patients (96.7xa0%) underwent exploration. Twenty-one (95.6xa0%) of those who underwent pancreatic tumor resection achieved negative margins, with none requiring vessel resection. One (3.3xa0%) patient was resected with microscopic positive margins. Median follow-up was 15.6xa0months (range, 6.3–26.1xa0months). Median and 1-year overall survival was 20xa0months and 91xa0%, respectively. Median and 1-year progression-free survival was 14.9xa0months and 61xa0%, respectively.ConclusionSBRT-based neoadjuvant therapy for BRPC is well tolerated and can result in a high rate of margin-negative tumor resection.

Outcomes of definitive or preoperative IMRT chemoradiation for esophageal cancer

ObjectivesIntensity-modulated radiation therapy (IMRT) is evolving for the treatment of gastrointestinal cancers. The purpose of this study is to analyze our outcomes utilizing IMRT chemoradiation for esophageal cancer.MethodsIMRT was incorporated into esophageal cancer treatment at our center in 2006. Patients treated between 2006 and 2011 with either preoperative or definitive IMRT chemoradiation to 50–60xa0Gy prescribed to the gross tumor volume and 45–50.4xa0Gy to the clinical target volume concurrently with chemotherapy were evaluated. IMRT techniques included multifield segmented step and shoot, compensator-based, and volumetric arc therapy. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan–Meier and log-rank analysis. Multivariate analysis (MVA) for OS and DFS were performed with a Cox proportional hazard ratio model.ResultsWe identified 108 patients with a median follow-up of 19xa0months. Median OS and DFS were 32 and 21.6xa0months, respectively. Fifty-eight (53.7xa0%) patients underwent surgical resection. There was no difference in OS or DFS in patients who underwent surgery compared to patients treated definitively without surgery. Median weight loss was 5.5xa0%. Rates of hospital admissions, feeding tube placement, stent placement, dilation, and radiation pneumonitis were 15.7, 7.4 4.6, 12, and 1.9xa0%, respectively. Long-term radiation pneumonitis was observed in six (5.6xa0%) patients. MVA revealed that age, stage, and surgery were prognostic for DFS, while gender and histology were not. Gender, histology, and stage were prognostic of OS on MVA, while surgery and age were not.ConclusionsIMRT chemoradiation for esophageal cancer is safe and effective when compared to published series of 2D or 3D conformal radiation therapy. This is the largest single institutional series with long-term follow-up, confirming that IMRT is a viable treatment option for the curative treatment of esophageal cancer.

Effect of prophylactic fluconazole on oral mucositis and candidiasis during radiation therapy for head-and-neck cancer

PURPOSEnRadiation therapy (RT) or chemoradiation therapy (CRT) for carcinoma of the head and neck can result in high rates of candidiasis and mucositis. Prophylactic fluconazole (FCZ) has been shown to reduce the incidence of candidiasis. We report our outcomes of patients with head-and-neck cancer undergoing CRT treated prophylactically with FCZ.nnnMETHODS AND MATERIALSnAn institutional review board-approved database of head-and-neck cancer patients treated with RT or CRT was reviewed to identify patients treated between 2004 and 2009 who received at least 50 Gy to approximately two-thirds of the oral cavity or oropharynx mucosa. Eligible patients were divided into 2 groups: the usual care group and the prophylaxis group. The primary endpoints were the incidence of mucositis and candidiasis.nnnRESULTSnA total of 181 patients were eligible for analysis: 72 patients in the prophylactic group and 109 patients in the usual care group. Patient characteristics and radiation dose were comparable between groups. RT alone was given in 28 patients (16%). Mucositis data were available in 161 (89%) patients. Grade 2 or higher mucositis was seen in 131 (81%) patients. Prophylactic FCZ had significantly decreased grade 2 or higher mucositis. In the usual care group and prophylaxis group patients, 83 of 93 patients (89.3%) and 48 of 68 patients (70.6%), respectively, developed grade 2 or higher mucositis (P = .003).nnnCONCLUSIONSnProphylactic administration of FCZ twice weekly during CRT for head-and-neck cancer reduces incidence of mucositis and thrush.