Intensity-Modulated Radiation Therapy vs. 3D Conformal Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: We compared our institutional experience using 3D conformal radiation therapy (3DCRT) vs. IMRT (intensity-modulated radiation therapy) for anal cancer. METHODS: We performed a single-institution retrospective review of all patients with squamous cell carcinoma anal cancer treated from September 2000 through September 2011, using definitive chemoradiation with curative intent. RESULTS: This study included 89 consecutive patients (37 3DCRT, 52 IMRT). Median follow-up for all patients, IMRT patients alone, and CRT patients alone was 26.5 months (range, 3.5-133.6), 20 months (range, 3.5-125.5), and 61.9 months (range, 7.6-133.6), respectively. Three-year overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and colostomy-free survival (CFS) were 91.1%, 82.3%, 90.8%, and 91.3% in the IMRT cohort and 86.1%, 72.5%, 91.9%, and 93.7% in the 3DCRT group (all P > .1). More patients in the 3DCRT group required a treatment break (11 vs. 4; P = .006), although the difference in median treatment break duration was not significant (12.2 vs. 8.0 days; P = .35). Survival did not differ based on whether a treatment break was needed (all P > .1). Acute grade ≥3 nonhematologic toxicity was decreased in the IMRT cohort (21.1 vs. 59.5%; P < .0001). Acute grade ≥3 skin toxicity was worse in the 3DCRT group (P < .0001), whereas an improvement in late grade ≥3 gastrointestinal (GI) toxicity was observed in the IMRT patients (P = .012). CONCLUSIONS: This study is the largest thus far to compare 3DCRT and IMRT for definitive treatment of anal cancer. Although long-term outcomes did not significantly differ based on RT technique, a marked decrease in adverse effects and the need for a treatment break was achieved with IMRT.

Lymph node harvest in esophageal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT). METHODS: An 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. RESULTS: We identified 358 patients with a mean follow-up of 27.3 months. 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 65.6 months and 52.7%, 29.7 months and 30.4%, and 17.7 months and 25.4% (p=0.0002). 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. CONCLUSIONS: The 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.

Minimally invasive surgery for esophageal cancer: review of the literature and institutional experience.

BACKGROUND: Esophageal cancer represents a major public health problem in the world. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and surgeons experienced in minimally invasive procedures. METHODS: The authors reviewed the most recent and largest studies published in the medical literature that reported the outcomes for MIE techniques. RESULTS: In larger series, MIE has proven to be equivalent in postoperative morbidity and mortality to the open esophagectomy. However, MIE has been associated with less blood loss, reduced postoperative pain, decreased time in the intensive care unit, and shortened length of hospital stay compared with the conventional open approaches. Despite limited data, no significant difference in survival stage for stage has been observed between open esophagectomy and MIE. CONCLUSIONS: The myriad of MIE techniques complicates the debate for defining the optimal surgical approach for the treatment of esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.

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

PURPOSE: Stereotactic 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. METHODS AND MATERIALS: A 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). RESULTS: Seventy-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%). CONCLUSIONS: SBRT 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.

Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors.

PURPOSE: The American Joint Committee on Cancer (AJCC) staging manual has introduced a TNM staging classification for jejunal-ileal (midgut) neuroendocrine tumors (NETs). This classification has not been validated in a population consisting solely of midgut NETs. The purpose of this study was to test the prognostic validity of the classification in such a population. METHODS: Patients with jejunal and ileocecal NETs who were treated at the Moffitt Cancer Center between 2000 and 2010 were assigned stages (I through IV). Kaplan-Meier analyses for overall survival (OS) were performed on the basis of TNM stage and pathologic grade. Multivariate modeling was performed using Cox proportional hazards regression. RESULTS: We identified 691 patients with jejunal-ileocecal NETs. The AJCC classification in aggregate was highly prognostic for OS (P < .001). Five-year OS rates for stages I through IV were 100%, 100%, 91%, and 72%, respectively. The survival difference between stages III and IV was significant (P < .001); the difference between stages I/II versus III was not statistically significant (P = .1). Among patients with stage IIIB tumors, 5-year survival rates were 95% for resectable tumors versus 78% for unresectable mesenteric tumors (P = .02). A proliferative threshold of five mitoses per 10 high-power fields (HPF) was of greater prognostic value than a threshold of two mitoses per 10 HPF for discriminating between low- and intermediate-grade tumors. CONCLUSION: Stage I and II midgut NETs are associated with identical survival rates. Stage IIIB tumors are heterogeneous, with significant differences in survival observed between resectable mesenteric lymph nodes versus unresectable masses in the root of the mesentery. A higher mitotic cutoff of five per 10 HPF may lead to improved prognostic differentiation between low- and intermediate-grade tumors. Revisions to the current AJCC staging and grading classification may be warranted.

Relapse-free survival in patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging classifications.

BACKGROUND: The risk of metastatic spread among patients with early-stage pancreatic neuroendocrine tumors has not been well established. The authors sought to evaluate whether the new TNM staging systems proposed by the American Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society (ENETS) are prognostic for relapse-free survival (RFS) after surgical resection. METHODS: Patients with surgically resected localized or locally advanced pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I-III) based on the AJCC and ENETS classifications. RFS and overall survival were measured using Kaplan-Meier methodology, with log-rank testing for evaluation of the 2 tumor staging systems. Multivariate analysis was performed controlling for tumor grade, location, surgery type, functional hormonal status, and incidental diagnosis. RESULTS: The authors identified 123 patients with nonmetastatic, surgically resected pancreatic NETs. When using the AJCC classification, 5-year RFS rates for stages I through III were 78%, 53%, and 33%, respectively (P < 0.01). Using the ENETS classification, 5-year RFS rates for stages I to III were 100%, 70%, and 53% (P < 0.18). When excluding patients who were referred after their metastatic recurrence, the 5-year RFS rates for stages I to III were 90%, 73%, and 66% according to the AJCC classification, and 100%, 84%, and 75% according to the ENETS classification. Recurrence rates peaked at approximately 2 years after surgery. CONCLUSIONS: The AJCC and ENETS TNM classifications for pancreatic NETs are prognostic for recurrence-free survival and can be adopted in clinical practice.

Pathologic nonresponders after neoadjuvant chemoradiation for esophageal cancer demonstrate no survival benefit compared with patients treated with primary esophagectomy.

BACKGROUND: Neoadjuvant chemoradiation (NCRT) has become the preferred treatment for patients with locally advanced esophageal cancer. Survival often is correlated to degree of pathologic response; however, outcomes in patients who are found to be pathologic nonresponders (pNR) remain uninvestigated. This study was designed to evaluate survival in pNR to NCRT compared with patients treated with primary esophagectomy (PE). METHODS: Using our comprehensive esophageal cancer database, we identified patients treated with NCRT and deemed pNR along with patients who proceeded to PE. Clinical and pathologic data were compared using Fisher's exact and χ(2), whereas Kaplan-Meier estimates were used for survival analysis. RESULTS: We identified 63 patients treated with NCRT and were found to have a pNR, and 81 patients who underwent PE. Disease-free (DFS) and overall survival (OS) were significantly decreased in the pNR group compared with those treated with PE (10 vs. 50 months (0-152), P < 0.001 and 13 vs. 50 months (0-152), P < 0.001, respectively). For patients with stage II disease, DFS and OS were similarly decreased in pathologic nonresponders (13 vs. 62 months (0-120), P < 0.001 and 31 vs. 62 months (0-120), P = 0.024, respectively). There were no differences in DFS or OS for patients with stage III disease (10 vs. 14 months (0-152), P = 0.29 and 10 vs. 19 months (0-152), P = 0.16, respectively). CONCLUSIONS: Pathologic nonresponders to NCRT for esophageal cancer receive no benefit in DFS or OS compared with patients treated with PE. For patients with stage II disease, DFS and OS are, in fact, significantly decreased in the pNR.

An elevated body mass index does not reduce survival after esophagectomy for cancer.

BACKGROUND: Incidences of esophageal cancer and obesity are both rising in the United States. The aim of this study was to determine the influence of elevated body mass index on outcomes after esophagectomy for cancer. METHODS: Overall and disease-free survivals in obese (BMI ≥ 30), overweight (BMI 25-29), and normal-weight (BMI 20-24) patients undergoing esophagectomy constituted the study end points. Survivals were calculated by the Kaplan-Meier method, and differences were analyzed by log rank method. RESULTS: The study included 166 obese, 176 overweight, and 148 normal-weight patients. These three groups were similar in terms of demographics and comorbidities, with the exception of younger age (62.5 vs. 66.2 vs. 65.3 years, P = 0.002), and higher incidence of diabetes (23.5 vs. 11.4 vs. 10.1%, P = 0.001) and hiatal hernia (28.3 vs. 14.8 vs. 20.3%, P = 0.01) in obese patients. Rates of adenocarcinoma histology were higher in obese patients (90.8 vs. 90.9 vs. 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6 vs. 54.5 vs. 66.2%, P = 0.004). Response to neoadjuvant treatment, type of surgery performed, extent of lymphadenectomy, rate of R0 resections, perioperative complications, and administration of adjuvant chemotherapy were not influenced by BMI. At a median follow-up of 25 months, 5-year overall and disease-free survivals were longer in obese patients (respectively, 48, 41, 34%, P = 0.01 and 48, 44, 34%, P = 0.01). CONCLUSIONS: In our experience, an elevated BMI did not reduce overall and disease-free survivals after esophagectomy for cancer.

Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer.

BACKGROUND: Esophageal cancer remains a malignancy with high morbidity and mortality despite improvements to diagnosis, staging, chemotherapy, radiation, and surgery. Neoadjuvant therapy (NT) may improve oncologic outcome in many patients, however the degree to which patients benefit remains unclear. We examined the relationship between pathologic response to NT and magnitude of benefit in patients with esophageal cancer. METHODS: Using a comprehensive esophageal cancer database, we identified patients who underwent esophagectomy between 1994 and 2008. Pathologic response was denoted as complete (pCR), partial (pPR), and nonresponse (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate, while Kaplan-Meier estimates were used for survival analysis. RESULTS: We identified 347 patients who underwent esophagectomy, and 262 (75.5%) were treated with NT. The median age was 66 years (28-86 years) with median follow-up of 20 months (1-177 months). There were 106 (40.5%) patients exhibiting pCR, 95 (36.3%) with pPR, and 61 (23.3%) with NR. The rate of R0 resections was higher amongst pCR (100%) compared with 94.7% in pPR (P = 0.02) and 87.5% in NR (P = 0.0007). There were 15 (14.2%) recurrences in pCR, 22 (23.7%) in pPR, and 17 (28.8%) in NR (P = 0.04). Patients achieving pCR had 5-year disease-free survival (DFS) and overall survival (OS) of 52% and 52%, respectively, compared with 36% and 38% in pPR and 22% and 19% in NR (P < 0.0001, P < 0.0001). CONCLUSIONS: Esophageal cancer patients frequently succumb to their disease. However, patients treated with neoadjuvant therapy who achieve pCR have a higher rate of R0 resections, fewer recurrences, and improved 5-year OS and DFS.

Correlations between neoadjuvant treatment, anemia, and perioperative complications in patients undergoing esophagectomy for cancer.

INTRODUCTION: The influence of preoperative hemoglobin levels on outcomes of patients undergoing esophagectomy for cancer is not clearly defined. The goal of this article was to explore the association between combined modality therapy, preoperative anemia status, and perioperative blood transfusion and risk of postoperative complications among patients undergoing esophageal resection. METHODS: From a retrospective esophageal database, 413 patients were identified. Anemia was defined according to the World Health Organization classification of <13 g/dL or <12 g/dL for men or women, respectively. Statistical analysis was performed with analysis of variance, Pearson's chi(2), or Fisher exact test as appropriate. The independent association of anemia, blood transfusion, and combined modality treatment on risk of postoperative complications were examined using multiple logistic regression. RESULTS: Information on combined modality treatment, preoperative hemoglobin levels, and blood transfusion was available for 413 patients, of whom 57% received combined modality treatment. Overall 197 (47.6%) patients were preoperatively found to be anemic, and those who had received combined modality treatment were more likely to be anemic (60.6% versus 30.7%, P < 0.001). Anemic patients required more blood transfusions than nonanemic patients (46.7% versus 29.6%, P < 0.001). Seventy-five percent of patients who required transfusion during the hospital stay had received combined modality treatment (P = 0.01). Combined modality treatment and anemia were not associated with increased risk of complications. Patients with any perioperative complication and surgical site infections were more likely to have received blood transfusion compared to patients without complications (OR = 1.73; 95% CI 1.04-2.87 and OR = 2.98; 95% CI 1.04-8.55; respectively). CONCLUSIONS: Overall, we determined that administration of neoadjuvant treatment to esophageal cancer patients was not associated with an increased rate of perioperative complications. Preoperative anemia did not predict worsened short-term outcomes, but increased the chances of red blood cell transfusion, which were significantly associated with higher overall complications and increased risk of surgical site infections. These data confirm previous studies that allogenic red blood cell transfusions are independent risk factors for increased morbidity and mortality and should be minimized during surgery for esophageal cancer.

Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer?

BACKGROUND: Esophageal cancer continues to increase in incidence. Many patients are presenting with stage II or greater disease and proceeding to neoadjuvant chemoradiation therapy before resection. Approximately 30% of patients will achieve a complete response and might not benefit from proceeding to resection. This study will examine the ability of PET to predict patients with a complete pathologic response. STUDY DESIGN: A query of our IRB-approved esophageal database revealed 81 patients who underwent a pre- and postchemoradiation PET scan and then proceeded to esophageal resection. Statistical analysis was performed to determine the ability of PET to predict a complete pathologic response. RESULTS: When comparing posttherapy PET with final pathology, it was determined that PET could not consistently differentiate a complete pathologic response from patients who still had persistent disease. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.8%, 43.8%, 70%, 35%, and 56%, respectively, for patients with a complete PET response after neoadjuvant therapy. CONCLUSIONS: A complete PET response after neoadjuvant chemoradiation is not substantially predictive of a complete pathologic response. Patients should still be referred for resection unless distant metastases are identified.