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Purpose: To investigate the differences in baseline staging of anal squamous cell carcinoma based on CT, MRI, and PET/CT, and the resultant impact on the radiation plan., Methods: This retrospective study included consecutive patients with anal squamous cell carcinoma who underwent baseline pelvic MRI, CT, and PET/CT (all examinations within 3 weeks of each other) from January 2010 to April 2020. CTs, MRIs, and PET/CTs were re-interpreted by three separate radiologists. Several imaging features were assessed; tumor stage was determined based on the eight edition of the American Joint Committee on Cancer (AJCC) staging manual; and T (tumor), N (node), and M (metastasis) categories were determined based on National Comprehensive Cancer Network (NCCN) guidelines. Radiologist assessments were then randomly presented to a radiation oncologist who formulated the radiation plan in a blinded fashion., Results: Across 28 patients (median age, 62 years [range, 31-78], T-category classification was significantly different on PET/CT compared to MRI and CT (p = 0.037 and 0.031, respectively). PET/CT staged a higher proportion of patients with T1/T2 disease (16/28, 57%) compared to MRI (11/28, 39%) and CT (10/28, 36%). MRI staged a higher proportion of patients with T3/T4 disease (14/28, 50%) compared to CT (12/28, 43%) and PET/CT (11/28, 39%). However, there was no significant difference between the three imaging modalities in terms of either N-category, AJCC staging, or NCCN TNM group classification, or in treatment planning., Conclusion: Our exploratory study showed that MRI demonstrated a higher proportion of T3/T4 tumors, while PET/CT demonstrated more T1/T2 tumors; however, MRI, CT, and PET/CT did not show any significant differences in AJCC and TNM group categories, nor was there any significant difference in treatment doses between them when assessed independently by an experienced radiation oncologist., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate safety and efficacy of radiation segmentectomy (RS) with 90 Y glass microspheres in patients with limited metastatic liver disease not amenable to resection or percutaneous ablation., Methods: Patients with ≤ 3 tumors treated with RS from 6/2015 to 12/2017 were included. Target tumor radiation dose was > 190 Gy based on medical internal radiation dose (MIRD) dosimetry. Tumor response, local tumor progression (LTP), LTP-free survival (LTPFS) and disease progression rate in the treated segment were defined using Choi and RECIST 1.1 criteria. Toxicities were evaluated using modified SIR criteria., Results: Ten patients with 14 tumors underwent 12 RS. Median tumor size was 3 cm (range 1.4-5.6). Median follow-up was 17.8 months (range 1.6-37.3). Response rates per Choi and RECIST 1.1 criteria were 8/8 (100%) and 4/9 (44%), respectively. Overall LTP rate was 3/14 (21%) during the study period. One-, two- and three-year LTPFS was 83%, 83% and 69%, respectively. Median LTPFS was not reached. Disease progression rate in the treated segment was 6/18 (33%). Median overall survival was 41.5 months (IQR 16.7-41.5). Median delivered tumor radiation dose was 293 Gy (range 163-1303). One major complication was recorded in a patient post-Whipple procedure who suffered anaphylactic reaction to prophylactic cefotetan and liver abscess in RS region 6.5 months post-RS. All patients were alive on last follow-up., Conclusion: RS of ≤ 3 hepatic segments can safely provide a 2-year local tumor control rate of 83% in selected patients with limited metastatic liver disease and limited treatment options. Optimal dosimetry methodology requires further investigation.

Background: The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD)., Methods: Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990-1999, 2000-2004, 2005-2009, 2010-2014) were evaluated and compared., Results: The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001)., Conclusions: Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

Background: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial., Methods: Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality., Results: Among 209 consecutive patients who underwent pancreatectomy, 159 (76 %) experienced at least one adverse event within 90 postoperative days. Patients who received preoperative chemoradiation (n = 137, 66 %) were more likely to have borderline resectable/locally advanced tumors, to have received induction chemotherapy, and to require vascular resection at pancreatectomy than those who did not receive chemoradiation (all P < 0.05). Nonetheless, there were no significant differences in the rates of severe complications, readmission, or mortality between these groups (all P > 0.05). Among patients who underwent pancreatoduodenectomy, the rate of pancreatic fistula was similar between those who received chemoradiation and those who did not (P = 0.96). In contrast, those who received chemoradiation prior to distal pancreatectomy had a lower rate of pancreatic fistula (P < 0.01)., Conclusion: Preoperative chemoradiation is not associated with an increase in 90-day morbidity or mortality, and it may reduce the rate of pancreatic fistula following distal pancreatectomy.

Purpose: The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC., Methods: Patients who underwent extended surgery for GBC at Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University, University of Michigan, and University of Texas MD Anderson between 1985 and 2008 were reviewed. Patients with metastatic disease at surgery, gross residual disease, or missing pathologic information were excluded., Results: Of the 112 patients identified, 61 % received adjuvant radiation, 93 % of whom received concurrent chemotherapy. Median follow-up of surviving patients was 47.3 (range 2.2-167.7) months. Patients who received adjuvant radiation had a higher rate of advanced T-stage (57 vs. 16 %, p < 0.01), lymph node involvement (63 vs. 18 %, p < 0.01), and positive microscopic margins (37 vs. 9 %, p < 0.01) compared with patients managed with surgery alone, but overall survival (OS) was comparable between the two cohorts (5-year OS: 49.7 vs. 52.5 %, p = 0.20). Lymph node involvement had the strongest association with poor OS (p < 0.01). Adjuvant radiation was associated with decreased isolated local failure (hazard ratio 0.17, 95 % confidence interval 0.05-0.63, p = 0.01). However, 71 % of recurrences included distant failure., Conclusions: Following oncologic resection for GBC, adjuvant radiation may offer improved local control compared with observation. The benefit of adjuvant radiation beyond chemotherapy alone should therefore be explored. Certainly, the high rate of distant failure highlights the need for more effective systemic therapy.

Background: Preoperative/neoadjuvant therapy (NT) is increasingly utilized for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, little data exist regarding information on the use of additional postoperative therapy following NT. The lymph node ratio (LNR) is a prognostic marker of oncologic outcomes after NT and resection. In this study, we evaluated the effectiveness of postoperative therapy following NT, stratified by LNR., Methods: A prospective tumor registry database was queried to identify patients with PDAC who underwent resection following NT from 1990 to 2008. Clinicopathologic factors were compared to identify associations with overall survival (OS) and time to recurrence (TTR) based on postoperative chemotherapy status., Results: Thirty-six (14 %) of the 263 patients received additional postoperative therapy. No differences were observed in the pathologic characteristics between patients who received postoperative chemotherapy and those who did not. The median LNR was 0.12 for patients with N + disease. Following NT, the administration of postoperative therapy was associated with improved median OS (72 vs. 33 months; p = 0.008) for patients with an LNR < 0.15. There was no association between postoperative chemotherapy and OS for patients with LNR ≥ 0.15. Multivariate analysis demonstrated that the administration of postoperative systemic therapy in patients with a low LNR was associated with a reduced risk of death (hazard ratio 0.49; p = 0.02)., Conclusion: Postoperative chemotherapy after NT in patients with low LNR is associated with improved oncologic outcomes.

Background: Local tumor control (LC), overall survival (OS), symptom palliation, and late toxicity for patients with locally recurrent anorectal cancer treated with a computed tomography (CT)-guided interstitial brachytherapy implant were examined., Methods: The medical records of 20 consecutive patients who had received interstitial brachytherapy for locally recurrent anorectal cancer from 2000 through 2012 were reviewed. Seventeen patients (85 %) had rectal cancer and three had anal cancer [median follow-up time for living patients, 23 months (range 13-132)]. Brachytherapy was used most commonly at the second pelvic recurrence (n = 13, 65 %). The implant dose was prescribed to 80 Gy to a 1-cm margin or 120 Gy to 100 % of the gross tumor volume. Endpoints were OS, LC, toxicity, and symptom palliation rate, all calculated from the time of implant., Results: The actuarial 1-year rates of LC and OS were 80 and 95 %, respectively. At presentation, 17 patients (85 %) had symptoms related to the treated tumor which were palliated in 13 patients (76 %) at a median time of 3 months (range 1-6); palliation was permanent for seven patients (54 %), and the other six patients lost palliation after a median 8 months (range 5-17). One patient experienced a grade 3 late complication requiring a stent for hydronephrosis; five had grade 2 toxicity, and four had grade 1 toxicity., Conclusions: CT-guided interstitial brachytherapy for locally recurrent anorectal tumors produced durable tumor control and long-term survival, with effective palliation and minimal long-term morbidity.

Background: The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases., Methods: A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression., Results: Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01-0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node., Conclusions: Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

Background: Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric-portal vein (SMV-PV) resection and the presence of histologic vein invasion., Methods: All patients who underwent pancreaticoduodenectomy from 2004 to 2011 at the authors' institution were identified. Preoperative pancreatic protocol CT images were re-reviewed to characterize the extent of tumor-vein circumferential interface (TVI) as demonstrating no interface, ≤ 180° of vessel circumference, >180° of vessel circumference, or occlusion. Findings were correlated with the need for venous resection, histologic venous invasion, and survival., Results: A total of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98 (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received neoadjuvant chemoradiation. The TVI classification system predicted with fair accuracy both the need for SMV-PV resection at the time of surgery and histologic invasion of the vein. In particular, 89.5 % of patients with TVI > 180° or occlusion required SMV-PV resection. Of those, 82.4 % had documented histologic SMV-PV invasion. TVI ≤ 180° was associated with favorable overall survival compared to a greater circumferential interface., Conclusions: A tomographic classification of the tumor-SMV-PV interface can predict the need for venous resection, pathologic venous involvement, and survival. To assist in treatment planning, a standardized assessment of this anatomic relationship should be routinely performed.

Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC (p = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk.

Background: In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer., Methods: A decision analytic model was constructed to compare the 2 approaches. Data from the National Cancer Database, National Surgical Quality Improvement Program, and literature populated the surgery-first arm. Data from our prospectively maintained institutional pancreatic cancer database populated the neoadjuvant arm. Costs were estimated by Medicare payment (2011 U.S. dollars). Survival was reported in quality-adjusted life-months (QALMs)., Results: The neoadjuvant chemoradiation arm consisted of 164 patients who completed preoperative therapy. Of these, 36 (22 %) did not proceed to surgery; 12 (7 %) underwent laparotomy but had unresectable disease; and 116 (71 %) underwent definitive resection. The surgery-first approach cost $46,830 and yielded survival of 8.7 QALMs; the neoadjuvant chemoradiation approach cost $36,583 and yielded survival of 18.8 QALMs. In the neoadjuvant arm, costs and survival times for patients not undergoing surgery, those with unresectable disease at laparotomy, and those completing surgery were $12,401 and 7.7 QALMs, $20,380 and 7.1 QALMs, and $45,673 and 23.4 QALMs, respectively., Conclusions: Neoadjuvant chemoradiation for pancreatic cancer identifies patients with early metastases or poor performance status, who can be spared an ineffective or prohibitively morbid operation, and is associated with improved survival at significantly lower cost than a surgery-first approach. Neoadjuvant chemoradiation followed by surgery is a strategy that provides more cost-effective care than a surgery-first approach.

Background: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG)., Methods: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity., Results: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older., Conclusions: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.

Background: For ampullary carcinoma (AC), the lymph node ratio (LNR) has been associated with overall survival. However, the use of the LNR to predict distant recurrence risk remains unknown. The purpose of this study was to determine if the LNR is associated with distant recurrence risk., Methods: One hundred forty three patients with AC who underwent pancreaticoduodenectomy between 1989 and 2011 were identified from a single-institution prospective database. Data on clinicopathologic factors and recurrence were analyzed., Results: At a median follow-up of 43 months (62 months for survivors), 55 patients (38 %) had developed recurrent disease, with a median time to recurrence of 13 months. Patients with a LNR ≥ 0.15 were more likely to have T3/4 tumors, advanced stage lymphovascular (LVI), or perineural invasion (PNI) and develop recurrent disease. Univariate analysis demonstrated that T-stage, lymph node status, AJCC stage, LVI, PNI, and LNR were significantly associated with decreased time to distant recurrence (TTDR). In multivariate stepwise regression, only LNR and LVI were significantly associated with decreased TTDR., Conclusions: A high positive LNR is associated with distant recurrence after surgical resection of AC. Given the high risk of disease recurrence, consideration for adjuvant therapy is warranted in patients with a LNR ≥ 0.15.

Background: We previously introduced a classification system for patients with localized pancreatic adenocarcinoma that integrates assessments of tumor anatomy, cancer biology, and patient physiology. By means of this system, we sought to analyze outcomes of patients with resectable anatomy but heterogeneous biology and physiology who were treated with neoadjuvant therapy., Methods: We evaluated consecutive patients (2002-2007) with anatomically potentially resectable cancers treated with chemotherapy or chemoradiation before potential pancreatectomy. We compared clinical factors and outcomes of patients classified as having disease that was clinically resectable (CR; no extrapancreatic disease, preserved performance status); suspicion for extrapancreatic disease (BR-B); or marginal performance status or significant comorbidity (BR-C). Patients with borderline resectable anatomy (BR-A) were excluded., Results: Resection rates for 138 CR, 41 BR-B, and 38 BR-C patients were 75, 46, and 37%, respectively (P < 0.001). Metastases, detected during treatment in 23% of patients, were the most common contraindication to resection among CR (15%) and BR-B (46%) patients. Performance status rarely precluded surgery except among BR-C (32%) patients. Factors associated with selection against surgery were older age, poor performance status, pain, and therapeutic complications (P < 0.05). The median overall survival of all patients was 21 months. Resected and unresected BR-B and BR-C patients had median overall survival durations similar to those of resected and unresected CR patients, respectively (P > 0.22)., Conclusions: This system describes discrete clinical subgroups of patients with pancreatic cancer who have similar, potentially resectable tumor anatomy but heterogeneous physiology and cancer biology. It may be used with neoadjuvant therapy to predict outcomes, individualize treatment algorithms, and optimize survival.

Objectives: To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma., Methods: One hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the "superior mesenteric artery (SMA) margin distance" between cancer cells and the superior mesenteric artery was employed., Results: Seventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of ≤1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis., Conclusions: Preoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control.

Purpose: We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy., Methods: Patients with a performance status of 0 or 1 were enrolled to receive interferon-alfa-2b (3 million units MWF), cisplatin (30 mg/m(2), 6 doses) and 5-fluorouracil (5-FU; 175 mg/m(2)/day), concurrent with external-beam radiation (50.4 Gy) and followed by 2 courses of systemic 5-FU. The protocol was modified to include an optional 9 day break in the middle of chemoradiation. Quality of life was assessed by use of validated instruments., Results: Twenty-eight patients were eligible for analysis. The operation of 15 (54%) patients was performed at other institutions. All patients had T3 tumors, 22 (79%) had positive lymph nodes and 4 (14%) had positive (R1) margins. 24 (86%) patients completed therapy. In all, 25 (89%) patients experienced grade 3 toxicity and 3 (11%) patients were hospitalized. The most common grade 3 events were leukopenia (15, 54%) and neutropenia (12, 43%). No grade 4 toxicity occurred. Overall quality of life decreased during chemoradiation but returned to baseline thereafter and was stable throughout surveillance. 19 patients have died; the median follow-up of the 9 survivors is 62 months. The median OS duration of treated patients was 42.3 (95% confidence interval 30.5-54.2) months., Conclusions: Adjuvant interferon-based chemoradiation can be delivered safely and tolerably-though with substantial reversible toxicity-to patients of good performance status at an experienced cancer center. Therapy may be associated with an improvement in overall survival.

Purpose: The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials., Patients and Methods: We analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level., Results: We enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74)., Conclusions: Although the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.

Background: We previously reported 26 patients who underwent preoperative chemoradiotherapy (CXRT) for T3 rectal cancer and were subsequently offered full-thickness local excision (LE) as an alternative to total mesorectal excision (TME). At nearly 4 years' follow-up, no difference in outcome was observed. This study compares outcomes in a larger cohort of patients and reevaluates the original 26 patients after longer follow-up., Methods: Retrospective review was performed of patients who underwent preoperative CXRT (radiation doses of 45, 50.4, or 52.5 Gy with concurrent 5-fluorouracil-based chemotherapy) followed by surgery for T3 rectal cancer. Forty-seven patients underwent LE (Kraske [n = 6] or transanal excision [n = 41]). 473 patients underwent TME (abdominoperineal resection [n = 141] or low anterior resection [n = 332]). Local recurrence, disease-free survival (DFS), disease-specific survival, and overall survival (OS) rates were compared., Results: Median follow-up was 63 months for the LE group and 59 months for the TME group. Twenty-three LE patients (49%) had a complete response to CXRT, 17 (36%) had microscopic residual disease, and 7 (15%) had gross residual disease, compared with 108 (23%), 89 (19%), and 276 (58%) TME patients, respectively. There was no significant difference between the 10-year actuarial local recurrence rate for the LE group versus the TME group (10.6% and 7.6%, respectively; P = .52), and no significant difference in DFS, disease-specific survival, or OS rates between groups., Conclusions: In selected patients who demonstrate an excellent response to preoperative CXRT for T3 rectal cancer, full-thickness LE offers comparable local control, DFS, and OS to that achieved with proctectomy and TME.

Introduction: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy., Methods: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed., Results: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival., Conclusions: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.

Background: Patients with resected extrahepatic bile duct adenocarcinoma who have microscopically positive resection margins and/or pathologic locoregional nodal involvement (R1pN1) have a high-risk of locoregional recurrence, and therefore, we advocate the use of adjuvant chemoradiation. To evaluate the safety and effectiveness of this treatment, we compared survival and side effects outcomes between such patients and patients with negative resection margins and pathologically negative nodes (R0pN0) who did not receive adjuvant treatment., Methods: Between 1984 and 2005, 65 patients were treated with curative-intended resection for extrahepatic bile duct adenocarcinoma. Patients with tumors arising in the gallbladder and periampullary region were excluded. Pathology and diagnostic images were centrally reviewed. Overall survival and locoregional recurrence outcomes for patients with standard-risk R0pN0 (surgery alone, or S group, n = 23) were compared with those of patients with high locoregional recurrence risk, R1 and/or pN1 (R1pN1) status who received adjuvant chemoradiation (S-CRT group, n = 42)., Results: The median follow-up for the entire group was 31 months. Patients in the S-CRT and S groups had a similar 5-year overall survival (36% vs. 42%, P = .6) and locoregional recurrence (5-year rate: 38% vs. 37%, P = .13). In the S-CRT group, three patients (7%) experienced an acute (grade 3 or more) side effect., Conclusions: Our finding of a lack of a survival difference between the S and S-CRT groups suggests that for patients with extrahepatic bile duct adenocarcinoma at high risk for locoregional recurrence (i.e., R1 resection or pN1 disease), adjuvant chemoradiation provides an equivalent overall survival despite of these worse prognostic features.

Background: Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX-CTXRT). However, the influence of CTX-CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX-CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma., Methods: A prospectively collected database on 71 consecutive patients who underwent CTX-CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis., Results: Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50-50.6)] and body mass index (BMI) of 26 kg/m(2) or above [relative risk 4.08 (95% confidence interval 1.08 to 15.4)] were significant risk factors for overall complications., Conclusions: CTX-CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.

Background: The standard treatment for epidermoid carcinoma of the anal canal consists of combined radiation and chemotherapy. For patients who present with persistent or locally recurrent disease, salvage abdominoperineal resection is the treatment of choice. The purpose of this study is to review our experience with salvage surgery in this group of patients., Methods: From 1990-2002, 31 patients underwent radical salvage surgery with curative intent after failure of initial sphincter-conserving therapy, and the medical records of these patients were retrospectively reviewed. Clinicopathologic variables were determined and comparisons performed with the Cox proportional hazards model. Survival was calculated by the Kaplan-Meier method., Results: Eleven patients underwent radical salvage surgery for persistent disease and 20 patients for recurrent disease. The median follow-up time was 29 months. The actuarial 5-year overall survival was 64%. Twelve patients developed recurrent disease after radical salvage surgery. Patients who received an initial radiation dose of less than 55 Gy had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (5-year overall survival 37.5% vs. 75%; age-adjusted hazard ratio 8.2 [95% CI: 1.1-59.8], P = .037). The presence of positive lymph nodes at presentation also adversely affected survival (P < .05). Factors that were not found to have an impact on survival included the presence of persistent versus recurrent disease, tumor (T) stage, and margin status of resection., Conclusions: Long-term survival following salvage surgery for persistent or locally recurrent epidermoid carcinoma of the anal canal can be achieved in the majority of patients. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial chemoradiation therapy regimen have a worse prognosis after radical salvage surgery.

With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of "borderline resectability." In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.

Major vascular resection performed at the time of pancreaticoduodenectomy (PD) for adenocarcinoma remains controversial. We analyzed all patients who underwent vascular resection (VR) at the time of PD for any histology at a single institution between 1990 and 2002. Preoperative imaging criteria for PD included the absence of tumor extension to the celiac axis or superior mesenteric artery (SMA). Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. As a separate analysis, all patients who underwent PD with VR for pancreatic adenocarcinoma were compared to all patients who underwent standard PD for pancreatic adenocarcinoma. A total of 141 patients underwent VR with PD. Superior mesenteric-portal vein resections included tangential resection with vein patch (n=36), segmental resection with primary anastomosis (n=35), and segmental resection with autologous interposition graft (n=55). Hepatic arterial resections were performed in 10 patients, and resections of the anterior surface of the inferior vena cava were performed in 5 patients. PD was performed for pancreatic adenocarcinoma in 291 patients; standard PD was performed in 181 and VR in 110. Median survival was 23.4 months in the group that required VR and 26.5 months in the group that underwent standard PD (P=0.177). A Cox proportional hazards model was constructed to analyze the effects of potential prognostic factors (VR, tumor size, T stage, N status, margin status) on survival. The need for VR had no impact on survival duration. In conclusion, properly selected patients with adenocarcinoma of the pancreatic head who require VR have a median survival of approximately 2 years, which does not differ from those who undergo standard PD and is superior to historical patients believed to have locally advanced disease treated nonoperatively.

Background: For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors. and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head., Methods: Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence., Results: The overall median survival from the time of tissue diagnosis was 21 months (range 19-26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect., Conclusion: This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.

Pancreatic cancer is a lethal disease characterized by local invasion and early dissemination. It is resistant to conventional surgical, radiotherapeutic, and chemotherapeutic modalities. These interventions have had minimal impact on overall survival with very few patients enjoying long term survival. Over the past few years, 2'difluoro-2'deoxycytidine (gemcitabine) has demonstrated modest activity in this disease and investigations are proceeding to expand its role in combination with radiotherapy and other chemotherapeutic agents. In addition, the identification of the molecular defects underlying this disease has suggested molecular targets for the design of rational systemic therapy. These targets include matrix metalloproteinases, K-ras, HER2/neu, p53, and the epidermal growth factor receptor. Current and future clinical trials designed to improve the survival of patients with pancreatic cancer will be discussed.