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Objectives To evaluate the 30‐day hospital readmission rate, reasons, and risk factors for patients with cancer who were discharged to home setting after acute inpatient rehabilitation. Design, Setting, and Participants This was a secondary retrospective analysis of participants in a completed prospective survey study that assessed the continuity of care and functional safety concerns upon discharge and 30 days after discharge in adults. Patients were enrolled from September 5, 2018, to February 7, 2020, at a large academic quaternary cancer center with National Cancer Institute Comprehensive Cancer Center designation. Main Outcomes and Measures Thirty‐day hospital readmission rate, descriptive summary of reasons for readmissions, and statistical analyses of risk factors related to readmission. Results Fifty‐five (21%) of the 257 patients were readmitted to hospital within 30 days of discharge from acute inpatient rehabilitation. The reasons for readmissions were infection (20, 7.8%), neoplasm (9, 3.5%), neurological (7, 2.7%), gastrointestinal disorder (6, 2.3%), renal failure (3, 1.1%), acute coronary syndrome (3, 1.1%), heart failure (1, 0.4%), fracture (1, 0.4%), hematuria (1, 0.4%), wound (1, 0.4%), nephrolithiasis (1, 0.4%), hypervolemia (1, 0.4%), and pain (1, 0.4%). Multivariate logistic regression modeling indicated that having a lower locomotion score (OR = 1.29; 95% CI, 1.07–1.56; p = 0.007) at discharge, having an increased number of medications (OR = 1.12; 95% CI, 1.01–1.25; p = 0.028) at discharge, and having a lower hemoglobin at discharge (OR = 1.31; 95% CI, 1.03–1.66; p = 0.031) were independently associated with 30‐day readmission. Conclusion and Relevance Among adult patients with cancer discharged to home setting after acute inpatient rehabilitation, the 30‐day readmission rate of 21% was higher than that reported for other rehabilitation populations but within the range reported for patients with cancer who did not undergo acute inpatient rehabilitation., Short Abstract Research is needed to determine the rates of and risk factors for 30‐day hospital readmission after acute inpatient cancer rehabilitation to understand the nature of this problem and to decrease costs associated with readmissions. Among adult patients with cancer discharged to a home setting after acute inpatient rehabilitation, the 30‐day readmission rate of 21% was higher than that reported for other rehabilitation populations but within the range reported for patients with cancer who did not undergo acute inpatient rehabilitation. Cancer rehabilitation patients may have unique risk factors for readmission.

To compare outcomes of radical hysterectomy (RH) across age groups based on surgical approach: minimally invasive surgery (MIS) vs laparotomy (LP).Cross-sectional retrospective review (Canadian Task Force classification II-2).Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center.Patients with early-stage cervical cancer who underwent RH at a tertiary cancer center between 1990 and 2013.Patients were stratified by age group (50, 50-59, and ≥60 years) and by surgical approach (minimally invasive surgery [MIS] vs laparotomy [LP]).Patients with early-stage cervical cancer who underwent RH were retrospectively reviewed to obtain demographic data, surgical data, and clinical outcomes. We used the Fisher exact, Wilcoxon rank-sum, and Cochran-Mantel-Haenszel tests to compare categorical and continuous variables stratified by surgical approach and age group. A total of 548 patients were evaluated, including 427 (77.9%) who underwent LP (age50, 84.3%; 50-59, 11.2%; ≥60, 4.5%) and 121 (22.1%) who underwent MIS (age50, 71.9%; 50-59, 17.3%; ≥60, 10.8%). In the MIS group, 71 patients (58.7%) underwent laparoscopy and 50 (41.3%) underwent robotic surgery. Patients in the MIS group were significantly older and heavier than those in the LP group. The operative time was significantly longer in the MIS group. There was no between-group difference in intraoperative complications in any of the 3 age groups. LP patients had more infectious complications (respiratory, systemic, and wound) than MIS patients in the50-year age group (53.3% vs 21.8%). The difference between the LP and MIS groups with respect to the postoperative noninfectious complication rate was greatest in the ≥60-year age group (p = .0324).The between-group difference in postoperative noninfectious complication rate in the oldest age group was twice that in either of the other 2 age groups (p = .0324), even though the MIS patients were older, heavier, and had a longer operative time compared with the LP patients.

Over and under nutrition are associated with worse outcomes for children with leukemia and lymphoma, however, the molecular basis for this clinical observation is not well understood. Many chemotherapeutics used for leukemia treatment are known to generate oxidative stress in vitro, therefore, we evaluated redox status and diet in pediatric leukemia patients during therapy in order to ascertain relationships between nutrition and oxidative stress. Dietary intake and redox measures in peripheral blood mononuclear cells from 32 pediatric leukemia and lymphoma patients were collected over six months during treatment. Baseline measures when patients were off chemotherapy and subsequent assessments were collected after one, two and six months. Oxidative stress increased over time in all patients, consistent with chemotherapy-induced redox effects. Older and younger children showed significantly different baseline levels of reactive oxygen species, which increased over time in all age ranges. Diet was assessed at points proximal to oxidative stress measurements and revealed a novel association with consumption of animal protein, vegetable protein, and total protein intake. Our findings demonstrate that chemotherapy increases oxidative stress in pediatric leukemia patients, and raises the possibility that dietary protein or altered protein metabolism could contribute to clinical outcomes.

Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure.In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms.Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses.In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC.Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed.123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23).This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.

Objective Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. Methods In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry. Results Twenty patients completed the trial. Median age and BMI were 57years (range: 27–67) and 34.5kg/m 2 (range: 21.9–50.0). Median duration of metformin was 9.5days (range: 7–24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 ( p =0.046), omentin ( p =0.007), insulin ( p =0.012), C-peptide ( p =0.018), and leptin ( p =0.0035). Compared to baseline, post-treatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p =0.0002), decreased phospho-S6rp in 14/20 patients (70%, p =0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p =0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation. Conclusion In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.

Purpose We prospectively compared computed tomography (CT)– and magnetic resonance imaging (MRI)–based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. Methods and Materials Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identified the clinical and tumor factors associated with ( 1 ) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and ( 2 ) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. Results Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm 3 ) was larger than the mean MRI HR-CTV volume (35.1 cm 3 ; P t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours ( P P =.013). Conclusions We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.

Objectives Cervical cancer is the leading cause of cancer and related deaths among women in Mozambique. There is limited access to screening and few trained personnel to manage women with abnormal results. Our objective was to implement primary HPV screening in Mozambique and navigate women with abnormal results to appropriate diagnostic and treatment services. Methods We prospectively enrolled women aged 30 to 49 at Mavalane General Hospital in Maputo, Mozambique. All participants underwent a pelvic examination by a nurse and a cervical sample was collected and tested for HPV DNA using careHPV (Qiagen, Gaithersburg, MD, USA). Women who tested positive for HPV (HPV+) underwent visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) to assess eligibility for cryotherapy. All HPV+ women were treated with cryotherapy, loop electrosurgical excision procedure (LEEP), or referred for cancer management based on results. Results From April 2018 to February 2019, 427 women underwent HPV testing. The median age was 39 years. 86/426 patients (20.2%) were HIV positive. 93 patients (21.8%) were HPV+ and 97.8% (91/93) returned for VAT and treatment including cryotherapy (n=68, 74.7%), LEEP (n=10, 11.0%) and referral for cancer management (n=4, 4.4%). Treatment is pending in 9 patients for cryotherapy. Conclusions Cervical cancer screening with primary HPV DNA testing, including follow-up and treatment, was found to be feasible in Maputo, Mozambique. This study is ongoing to and includes training medical providers to diagnose and treat cervical preinvasive disease and cancer.

Background Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). Objective This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. Study Design A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute–designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. Results In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. Conclusion Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient’s self-reported pain and functional recovery compared with standard bupivacaine.

To estimate the response rate of gemcitabine, paclitaxel, and doxorubicin in patients with advanced urothelial carcinoma, we conducted a phase II clinical trial. Patients with renal insufficiency cannot receive standard cisplatin-based chemotherapy for urothelial carcinoma, and carboplatin-based regimens have proved unsatisfactory. Secondary end points for this study included overall survival, safety of the regimen, and safety of same-day pegfilgrastim dosing.A two-stage design was chosen with target response rate of 40%. Key inclusion criteria were metastatic or unresectable urothelial carcinoma, no prior chemotherapy, glomerular filtration rate60 mL/min, and no dialysis. Gemcitabine (900 mg/m(2)), paclitaxel (135 mg/m(2)), and doxorubicin (40 mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or optionally day 2.Forty patients were enrolled and 39 were treated. Median age was 72 years (range 51-89). There were 7 complete and 15 partial responses, for a response rate of 56.4% (95% confidence interval, 39.6-72.2). Most cycles (82.8%) were given with same-day pegfilgrastim. Notable grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (10.3% each). There were 4 episodes of neutropenic fever (4 of 198 cycles [2%]; 4 of 39 patients [10.3%]) and no treatment-related deaths. Median overall survival was 14.4 months.The combination of gemcitabine, paclitaxel, and doxorubicin is effective first-line chemotherapy for patients with advanced urothelial carcinoma and renal insufficiency. Neutropenic prophylaxis was acceptable whether pegfilgrastim was given immediately or 24 hours after chemotherapy.

Objective Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. Methods We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. Results Median age at diagnosis was 30years (range 5–46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2months (range, 0.1 to 210.7) with a median overall survival of 14.9months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. Conclusion Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations.

Objective To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. Methods This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. Results A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p

Objective The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. Methods A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions Results A total of 30 patients were included in the study. The median age was 40.4years (range; 26–60) and median body mass index (BMI) was 26.4kg/m 2 (range; 17.7–40.0). A total 22 patients had tumors Conclusion Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.

Objectives To determine if the ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is a prognostic variable in patients with node-positive endometrial cancer and the impact of adjuvant therapy on survival. Methods After institutional review board approval, a retrospective review of patients diagnosed as having stage IIIC endometrioid or mixed endometrioid endometrial cancer at a single institution from January 2000 through October 2011 was performed. Clinicopathologic and adjuvant treatment data were collected. Univariate and multivariate analysis were used to identify prognostic factors for progression-free (PFS) and overall survival. Results One hundred twenty-four patients with stage IIIC1 (n = 64) and IIIC2 (n = 60) endometrial cancer were included in the analysis. Median age was 60 years (range, 25–84 years), and median follow-up was 49.4 months (range, 0.1–301.6 months). Age >70 years was identified as a prognostic factor for worse PFS (P = 0.0002) and overall survival (P = 0.0002) on multivariate analysis. Patients in this cohort receiving any adjuvant radiotherapy showed improved PFS (hazard ratio [HR], 0.34; 95% CI, 0.13–0.90; P = 0.03) compared with those receiving any adjuvant chemotherapy (HR, 2.33; 95% CI, 1.16–4.65; P = 0.02). In a subgroup analysis, patients with at least 10 nodes removed (n = 81) with an LNR greater than 50% had a PFS of 25.2 months compared with 135.6 months with an LNR of 50% or less (HR, 3.87; 95% CI, 1.15–13.04; P = 0.03). Conclusions Lymph node ratio may define a subgroup of stage IIIC endometrial cancers at increased risk for recurrence. Adjuvant radiotherapy was associated with decreased recurrence risk.

Radical trachelectomy is considered standard of care in patients with early-stage cervical cancer interested in future fertility. The goal of this study was to compare operative, oncologic, and fertility outcomes in patients with early-stage cervical cancer undergoing open vs. minimally invasive radical trachelectomy.A retrospective review was performed of patients from four institutions who underwent radical trachelectomy for early-stage cervical cancer from June 2002 to July 2013. Perioperative, oncologic, and fertility outcomes were compared between patients undergoing open vs. minimally invasive surgery.A total of 100 patients were included in the analysis. Fifty-eight patients underwent open radical trachelectomy and 42 patients underwent minimally invasive surgery (MIS=laparoscopic or robotic). There were no differences in patient age, body mass index, race, histology, lymph vascular space invasion, or stage between the two groups. The median surgical time for MIS was 272min [range, 130-441min] compared with 270min [range, 150-373min] for open surgery (p=0.78). Blood loss was significantly lower for MIS vs. laparotomy (50mL [range, 10-225mL] vs. 300mL [50-1100mL]) (p0.0001). Nine patients required blood transfusion, all in the open surgery group (p=0.010). Length of hospitalization was shorter for MIS than for laparotomy (1day [1-3 days] vs. 4days [1-9 days]) (p0.0001). Three intraoperative complications occurred (3%): 1 bladder injury, and 1 fallopian tube injury requiring unilateral salpingectomy in the MIS group and 1 vascular injury in the open surgery group. The median lymph node count was 17 (range, 5-47) for MIS vs. 22 (range, 7-48) for open surgery (p=0.03). There were no differences in the rate of postoperative complications (30% MIS vs. 31% open surgery). Among 83 patients who preserved their fertility (33 MIS vs. 50 open surgery), 34 (41%) patients attempted to get pregnant. Sixteen (47%) patients were able to do so (MIS: 2 vs. laparotomy: 14, p=0.01). The pregnancy rate was higher in the open surgery group when compared to the MIS group (51% vs. 28%, p=0.018). However, median follow-up was shorter is the MIS group compared with the open surgery group (25months [range, 10-69] vs. 66months [range, 11-147]). To date, there has been one recurrence in the laparotomy group and none in the MIS group.Our results suggest that radical trachelectomy via MIS results in less blood loss and a shorter hospital stay. Fertility rates appear higher in patients undergoing open radical trachelectomy.

BACKGROUND Pediatric neuroendocrine tumors (NETs) are rare tumors. The purpose of this study is to report the clinical characteristics and outcomes of pediatric patients treated for NET at a single institution. PROCEDURE A retrospective record review. RESULTS There were 33 evaluable patients with median age of 17.9 years (range, 9.9 to 21.9 y) and predominantly females (58%). There were 17 patients with well-differentiated appendiceal NET, whereas 16 were nonappendiceal. Most common nonappendiceal sites were unknown primary (N=6) and pancreas (N=4). Majority of tumors were low grade (N=24, 73%) and small (T1, N=22, 67%). Nonappendiceal tumors were more likely to be larger or high-grade tumors (5/16, 31%), or with metastasis. All appendiceal NET patients underwent curative surgery. All patients who experienced treatment failure had nonappendiceal NET, despite prior chemotherapy in 8 of 9 patients. The 5-year overall survival rates for patients with appendiceal and nonappendiceal NET were 100% and 66% (95% CI, 45%-95%; P=0.006); and 5-year relapse-free survival rate for patients with appendiceal and nonappendiceal NET were 100% and 41% (95% CI, 22%-75%; P=0.002). CONCLUSIONS Well-differentiated appendiceal tumors were the most common pediatric NET and have an excellent prognosis. Better therapies are needed for patients with nonappendiceal NET.

Objective To describe both clinical and pathological response rates, survival, and predictors of survival when using contemporary perioperative chemotherapy and surgical resection for patients with regionally advanced squamous cell carcinoma (SCC) of the penis. Patients and Methods Retrospective review of all patients diagnosed with SCC of the penis and regional lymph node metastases that were treated with chemotherapy with the intent to undergo lymphadenectomy. Clinical and pathological responses were reported. Recurrence-free and overall survival was estimated using Kaplan–Meier analysis. Cox proportional hazards regression was used to assess factors for survival. Results In all, 61 patients were identified, of which 54 (90%) received chemotherapy with paclitaxel/ifosfamide/cisplatin. In all, 39 patients (65%) had either a partial (PR) or complete response (CR) to chemotherapy. The 5-year survival varied significantly (P = 0.045–0.001) among patients achieving a CR/PR (50%), stable disease (25%), and progression (7.7%). In all, 10 patients (16.4%) were rendered pN0 with combined therapy and 20 patients (33%) were alive and disease free at a median follow-up of 67 months, while 32 (52%) died from disease. Long-term survival was associated with response to chemotherapy and favourable pathological findings after resection. Conclusion Contemporary chemotherapy resulted in clinically significant responses among patients with regionally advanced penile cancer. About 50% of such patients with an objective response to chemotherapy who undergo consolidative lymphadenectomy will remain alive at 5 years.

The ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is an important prognostic factor in several solid tumors. The objective of this study was to determine if LNR can be used to define a high-risk category of patients with node-positive early stage cervical cancer.We performed a retrospective review of patients diagnosed with node-positive stage I or II cervical cancer who underwent radical hysterectomy and pelvic +/- para-aortic lymphadenectomy at MD Anderson from January 1990 to December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free (PFS) and overall survival (OS).Ninety-five patients met the inclusion criteria and were included in the analysis. Median total nodes removed were 19 (range 1-58), and median number of positive nodes was 1 (range 1-12). Fifty-eight patients (61%) received radiation with concurrent cisplatin and 27 patients (28%) received radiotherapy alone. Twenty-one (22%) patients recurred. On multivariate analysis, a LNR6.6% was associated with a worse PFS (HR = 2.97, 95% CI 1.26-7.02, p = 0.01), and a LNR7.6% with a worse OS (HR = 3.96, 95% CI 1.31-11.98, p = 0.01). On multivariate analysis, positive margins were associated with worse PFS (p = 0.001) and OS (p = 0.002), and adjuvant radiotherapy (p = 0.01) with improved OS.LNR appears to be a useful tool to identify patients with worse prognosis in node-positive early stage cervical cancer. LNR may be used in addition to pathologic risk factors to tailor adjuvant treatment in this population.

Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a ( Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0–47·3) for the SABR group and 35·4 months (18·9–40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017–1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0·69 [95% CI 0·21–2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). Interpretation SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Funding Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Purpose Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

Objectives To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. Methods After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays. Results Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58–4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05–13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05). Conclusions Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.

Objectives The study objective was to analyze the impact of prognostic factors, including treatment modality, on outcome in patients with advanced-stage uterine serous carcinoma (USC). Methods A retrospective review of patients diagnosed with stage III or IV USC between 1993 and 2012 was performed. Summary statistics were used to describe demographic and clinical characteristics. Overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier analysis. Cox proportional hazards regression was used to model the association of potential prognostic factors with OS and RFS. Results The study included 260 patients with median follow-up of 26.6months (range 1–172.8). Median age was 63years (range 30–88) and 52.3% had stage III disease. In all, 60% were treated with surgery followed by chemotherapy, 18.1% received surgery, chemotherapy, and radiotherapy, 11.5% had surgery and radiotherapy, and 10.4% had neoadjuvant chemotherapy. The overall complete response rate was 68.9%, and the cumulative incidence of recurrence was 82.7%. Treatment that included surgery, chemotherapy, and radiation and stage III disease were associated with improved RFS on multivariate analysis. For OS, therapy with surgery, chemotherapy, and radiation, mixed histology, and stage III disease were associated with better OS on multivariate analysis. Conclusions Patients with advanced-stage USC have a poor prognosis, regardless of clinical factors or treatment received. However, combination therapy that includes chemotherapy and radiation appears to be associated with improved survival in these women.

Introduction Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received more than or equal to 45 Gy to the thorax, with pretreatment estimates of more than or equal to 20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median TnI or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated ( p = 0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.

To determine risk factors associated with conversion to laparotomy for women undergoing robotic gynecologic surgery.The medical records of 459 consecutive robotic surgery cases performed between December 2006 and October 2011 by 8 different surgeons at a single institution were retrospectively reviewed. Cases converted to laparotomy were compared to those completed robotically. Descriptive statistics were used to summarize the demographic and clinical characteristics.Forty of 459 (8.7%, 95% CI 6.3%-11.7%) patients had conversion to open surgery. Reason for conversion included poor visualization due to adhesions (13), inability to tolerate Trendelenburg (7), enlarged uterus (7), extensive peritoneal disease (5), bowel injury (2), ureteral injury (1), vascular injury (1), bladder injury (1), technical difficulty with the robot (2), and inability to access abdominal cavity (1). 5% of cases were converted prior to docking the robot. On univariate analysis, preoperative diagnosis (p=0.012), non-White race (p=0.004), history of asthma (p=0.027), ASA score (p=0.032), bowel injury (p=0.012), greater BMI (p0.001), need for blood transfusion (p0.001), and expected blood loss (p0.001) were associated with conversion. On multivariate analysis, non-White race (OR 2.88, 95% CI 1.39-5.96, p=0.004), bowel injury (OR 35.40, 95% CI 3.00-417.28, p=0.005), and increasing BMI (OR 1.06, 95% CI 1.03-1.09, p0.001) were significantly associated with increased risk for conversion. Prior surgery was not associated with conversion to open surgery (p=0.347).Conversion to laparotomy was required for 8.7% of patients undergoing robotic surgery for a gynecologic indication. Increasing BMI and non-white race were identified as the two preoperative risk factors associated with conversion.

Background We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

Accelerated partial breast irradiation (APBI) has been used as an alternative to whole-breast irradiation as part of breast-conserving therapy. Indications and outcomes are topics of ongoing investigation. Previous publications have focused on early postoperative infections and reported low rates of delayed infection. We investigated the pattern of infection after catheter-based APBI at our institution.Patients who underwent single-entry catheter-based APBI were identified from an institutional prospective registry including data regarding comorbidities and outcomes. Time of infection was calculated from the date of definitive catheter insertion and classified as early (≤30 days) or delayed.A total of 91 breast cancer patients were treated with APBI and enrolled in the registry from 2009 to 2011. The median follow-up was 484 days. Breast infection occurred in 13 (14.3 %), with 3 (3.3 %) occurring within 30 days of catheter placement and 10 (11.0 %) in a delayed fashion. Four patients required hospital admission, five underwent percutaneous aspiration, and one underwent incision and drainage. Eight were treated as outpatients with oral antibiotics alone.Consistent with other reports, we found an overall infection rate of 14.3 % with single-entry catheter-based APBI. There were substantially fewer infections in the early postoperative period than reported elsewhere, but there were more delayed infections. The intensive follow-up in our study likely identified late infections that may not have otherwise been recognized. Vigilance for infectious complications must continue beyond the immediate treatment period in patients undergoing catheter-based APBI. These infections can range in severity but typically can be managed in an outpatient setting.

Purpose The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m 2 to 825 mg/m 2 orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer.

Background: Capecitabine is an established radiosensitizer in rectal and other cancers. We conducted a prospective single arm phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine and radiotherapy. Methods: Patients who had inoperable or marginally operable gross disease in the breast and/or lymph node(s) after chemotherapy or gross disease on the chest wall or in the regional lymphatics after mastectomy were eligible. Patients 1-9 received capecitabine 825 mg/m2 BID daily beginning on the first day of radiotherapy. Excess grade 3 toxicity (%) was observed; the protocol was amended and subsequent patients received drug only on radiation treatment days. Radiation dose was at the discretion of the treating physician (50Gy-72 Gy, with no more than 2.5 Gy/fraction). Response was assessed by a single physician using paired radiation planning CTs (pretreatment and on-treatment after 45 Gy). Clinical correlation to all other available imaging was also made. Kaplan-Meier curves were used to estimate overall survival (OS) and local recurrence-free survival (LRFS). Circulating tumor cells (CTCs) in blood were examined in consenting patients. Results: The trial was stopped early after an unplanned interim analysis prompted by slow accrual suggested futility independent of response. From 2009-2012, 32 patients were accrued; 26 completed protocol specific treatment (17 post-mastectomy radiation with gross nodes, 4 pre-op, 5 aggressive palliation) and are included in this analysis. Median follow up was 7.3 months (interquartile range 6.7 – 17.4). Nineteen patients (73%) had a partial or complete response. Fourteen patients (53.9%) experienced at least one grade 3 non-dermatitis toxicity including 7/9 treated with continuous dosing. Four inoperable patients were treated with pre-op radiation therapy and 3 converted to operable. None achieved a pCR or near pCR. One-year actuarial OS was 52%. There was no difference in OS comparing among PMRT vs. preoperative or palliative RT (P = 0.90). One-year actuarial local recurrence free survival among PMRT patients was 38%. Ten patients had triple negative (TN) receptor status. There was no difference in radiation response by receptor status (P = 0.56); however, treatment was deemed subjectively futile (i.e., converted to operable but death secondary to new widespread M1 disease immediately post-op) in 9 of the 10 patients with TN disease versus 6 of the 16 patients with non-TN disease (P = 0.014). Median OS and 1-yr actuarial OS, among non-TN vs. TN patients were not reached vs. 6.1 months and 77% vs. 10% (P < 0.001), respectively. Eight/fifteen patients tested were positive for CTCs. CTCs did not correlate to receptor status, futility of RT or OS. Conclusions: Capecitabine can be safely administered as a daily concurrent chemoradiation regimen with weekend holidays. However, in this small, prospective and selected cohort, concurrent chemoradiation with capecitabine was futile among patients with TN breast cancer. Alternative strategies are urgently needed in TN patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-08.

Purpose To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P =.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.

Primary carcinomas of the urethra (PCU) are rare and often advanced when diagnosed. Treatment standards are lacking. We studied treatment response and survival in a cohort of patients with PCU, with emphasis on modern platinum-containing chemotherapy regimens plus surgery for advanced disease.This was a retrospective chart review of consecutive patients with PCU seen by medical oncologists at our institution over a recent 5-year period. Outcome was measured as best response to chemotherapy. Kaplan-Meier estimates were generated for survival and Cox proportional hazard was used for prognostic factors for survival.The 44 patients (64% women) included had a median age at diagnosis of 66.5 years. The most prevalent histologic subtypes of PCU were squamous cell carcinoma and adenocarcinoma. At diagnosis, 43% already had lymph node-positive [lymph node (LN)+] disease, and 16% had distant metastases. The entire cohort's overall survival (OS) was 31.7 months. The response rate to platinum-containing neoadjuvant chemotherapy was 72%. Twenty-one patients with locally advanced or LN+ PCU underwent chemotherapy plus surgery. Their median OS from chemotherapy initiation was 25.6 months. Four of 9 patients (44%) with LN+ PCU at diagnosis were alive at our review, with a minimum follow-up of more than 3 years.Modern platinum-containing regimens appear to be effective in advanced PCU. Preoperative chemotherapy is associated with prolonged disease-free survival in a subgroup of LN+ cases.

Adult rhabdomyosarcoma (RMS) is a rare tumor that has inferior outcome compared to younger patient population. The present work aims to study the age-related differences in management of adolescents and adults with RMS. Under an institutional review board-approved protocol, we retrospectively analyzed 239 patients, 10 years of age and greater, diagnosed with RMS at MD Anderson Cancer Center from 1957 through 2003. Of the 239 patients, 163 patients were nonmetastatic with a median overall survival (OS) of 3.8 years (95% CI 2.8–7.6). In the multivariate analysis, age >50 was significantly associated with shorter OS and recurrence-free survival (RFS) for primary patients. Metastases were present in 76 patients, the median OS was 1.4 years. Approximately 13% of metastatic patients

The traditional Fletcher-Williamson tandem and ovoid brachytherapy applicators for treatment of cervical cancer have ovoid shields that reduce the dose to the bladder and rectum. However, these shields produce artifact on computed tomography (CT) that prevents acquisition of high-quality images. To address this limitation, we designed and tested a novel CT-compatible applicator with movable shields, called MDA(3).Fifteen patients with stage IB1-IIB cervical cancer requiring definitive radiation therapy were enrolled in a prospective pilot study to evaluate image quality with the MDA(3). Image quality was assessed by comparing an initial scan obtained with the shields shifted to minimize shield artifact to a second scan obtained with the shields in treatment position. The 2 scans were then compared by a radiation oncologist blinded to the image source. In addition, image quality was assessed by analysis of Hounsfield values in the normal tissues.The MDA(3) was successfully employed for intracavitary brachytherapy in 15 patients. CT images obtained with the shields shifted were superior to CT images obtained with the shields in treatment position in every case as evaluated by the radiation oncologist (P.0001). The presence of the shields in the treatment position significantly increased the mean Hounsfield values within the bladder (P = .002) and rectum (P = .001) due to high-density image artifact.This novel applicator provides a clinically feasible solution to overcome the limitation of lack of ovoid shields on currently available CT-compatible applicators.

Purpose The purpose of this study was to evaluate long-term outcomes for men with early stage prostate cancer treated with radical prostatectomy (RP) or brachytherapy (BT) at a single tertiary care center. Methods and Materials We retrospectively analyzed data from 371 men with clinical T1a–T2c disease with prostate-specific antigen level n = 279) or BT ( n = 92) at MD Anderson Cancer Center in 2000–2001. Biochemical recurrence–free survival (BRFS) and prostate cancer–specific survival rates were compared by treatment modality. Results The median followup time was 7.2 and 7.6 years for patients treated with RP and BT, respectively. Disease was upgraded from GS 6 to 7 after central review of the biopsy specimen for 36 men treated with RP (12.9%) and 15 men treated with BT (16.3%). After RP, GS was upgraded in 121 men (43.4%) between the centrally reviewed biopsy and the RP specimen. After RP, 5-year BRFS rates were 96.1% and 90.6% for low- and intermediate-risk disease, respectively ( p = 0.003). After BT, 5-year BRFS rates were 92.5% and 95.8% for low- and intermediate-risk disease, respectively ( p = 0.017). After RP or BT, 5-year BRFS rates were not significantly different with GS upgraded. Five-year prostate cancer–specific survival rates for patients with upgraded GS were 100% for both RP and BT. Conclusions Excellent disease control outcomes can be achieved after either RP or BT as monotherapy for men with early stage prostate cancer. Upgrading of GS from 6 to 7, either (3 + 4) or (4 + 3), did not predict for worse outcomes.

Purpose To determine the safety, tolerability and maximum tolerated dose (MTD) of addition of erlotinib to bevacizumab and capecitabine-based definitive chemoradiation (CRT) in unresectable pancreatic cancer. Methods Seventeen patients with CT-staged, biopsy-proven unresectable pancreatic cancer were enrolled between 3/2008 and 10/2010. Prior chemotherapy was permitted. Two patients each were enrolled at dose levels (DLs) 1–4 and 9 patients at DL 5. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose of each drug was escalated in 5 DLs using the continual reassessment method. Bevacizumab was escalated from 5mg/Kg q2weeks (DLs 1–4) to 10mg/Kg q2weeks (DL 5); daily erlotinib from 100mg/day (DLs 1–2) to 150 mg/Kg (DLs 3–5); and capecitabine from 400mg/m2 twice daily on days of radiation (DL 1) to 650mg/m2 (DLs 2–3) to 825 mg/m2 (DLs 4–5). Reassessment for potential resection was performed 6–8 weeks later. Results Sixteen patients received gemcitabine-based chemotherapy prior to CRT. With a median clinical follow-up of 10 months, no grade 3 toxicities were observed in DLs 1–4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrhea, 1 rash). No grade 4 or 5 toxicities were seen. DL 4 was selected as the MTD; therefore, the recommended doses in combination with radiation are: bevacizumab, 5mg/Kg q2weeks; erlotinib, 150 mg/Kg daily; and capecitabine, 825mg/m2 BID. Median survival was 17.4 months. Of the five patients who underwent resection, 4 were originally deemed locally advanced and 1 was borderline resectable. Three patients had excellent pathological response (2 complete response and 20% viable tumor) at surgery, and the 2 patients with complete response are still alive at 61 and 67 months of follow up with no local or distant failures. Conclusions This chemoradiation regimen at the recommended dose levels is safe and tolerable for patients with unresectable pancreatic cancer and merits further evaluation.

Women with early cervical cancer undergoing radical hysterectomy via minimally invasive surgery (MIS) have decreased blood loss and a shorter hospital stay compared with laparotomy. It remains unclear whether there is a difference in benefit to the patient between robotic surgery and traditional laparoscopy. We sought to compare postoperative analgesic and antiemetic requirements between the two approaches.After institutional review board approval, the medication administration records of all patients who underwent MIS radical hysterectomy for cervical cancer at MD Anderson Cancer Center were reviewed. Analgesic and antiemetic medication use as well as visual pain scores was recorded. Descriptive statistics and nonparametric tests were used to compare the groups undergoing laparoscopy (LRH) and robotic surgery (RRH).A total of 85 patients underwent MIS for early cervical cancer, 55 LRH and 30 RRH. Median age was older in the RRH (42 vs. 52 years, p = 0.001). There was no difference in median body mass index (26.9 vs. 26.8 kg/m(2), p = 0.71). Length of stay was significantly shorter in the RRH (2 vs. 1 day, p = 0.005). Total intravenous opioids administered were significantly higher in the LRH (26.7 mg morphine equivalents) compared with the RRH (10.7 mg morphine equivalents) (p = 0.001). There was no difference in visual pain scores or antiemetics given.Intravenous opioids administered were significantly less for RRH compared to LRH; however, there was no difference in visual pain scores. Prospective studies are being performed to evaluate quality of life in patients undergoing MIS for gynecologic cancers.

A continuous dosing schedule of aerosolized ribavirin has been used for respiratory syncytial virus (RSV) upper respiratory tract infection and lower respiratory tract infection (LRTI) but is associated with high cost and inconvenient administration. We conducted an adaptive randomized trial to evaluate the effectiveness of an intermittent dosing schedule of ribavirin versus that of a continuous dosing schedule of ribavirin in preventing RSV LRTIs in 50 hematopoietic stem cell transplant recipients or patients with hematologic malignancies. LRTI occurred in 3 patients (9%) receiving the intermittent schedule and in 4 (22%) receiving the continuous schedule, with a 0.889 posterior probability. Because the intermittent schedule is easy to administer and has a higher efficacy than the continuous schedule, we recommend the intermittent schedule for patients who are at risk for RSV LRTI. Clinical Trials Registration. NCT00500578.

UNLABELLED What's known on the subject? and What does the study add? Patients with positive lymph nodes at radical cystectomy have a poor prognosis. The actual outcome of patients varies based on many factors, among which lymph node density has emerged as being more informative than nodal status of TNM staging. We combined clinical data from two major cancer centres in the USA and identified patients with an adequate lymphadenectomy and no perioperative chemotherapy to understand the natural history of the disease. Using this information, we created prognostic tools incorporating lymph node density that can be used for risk stratification, patient counselling and clinical trial design. OBJECTIVE • To develop a clinical tool based on lymph node density (LND) for patient counselling after radical cystectomy and for design of clinical trials of adjuvant therapies after radical cystectomy. PATIENTS AND METHODS • Using pooled data from two comprehensive cancer centres, we identified patients with lymph node metastases after radical cystectomy who received an adequate lymph node dissection according to existing literature (resection of eight or more nodes). • Only patients who had not received neoadjuvant or adjuvant chemotherapy were included to ensure that prediction models were based on the natural course of the disease. • Thresholds for LND ranging from 5% to 35%, in 5% increments, were used to dichotomize the study population. Within each set of two groups, the Kaplan-Meier product-limit estimator was used to estimate disease-specific survival (DSS) for each group, and Cox proportional hazards regression was used to test the significance of differences in DSS between the group with higher LND and the group with lower LND. • Tables and graphs showing the relationship between LND categories and 2-year and 5-year estimated DSS were created to aid in clinical decision-making. RESULTS • LND was valuable as a tool for stratifying node-positive patients into different risk groups based on expected survival. • At each LND threshold from 10% to 35%, patients with higher LND had significantly worse DSS than patients with lower LND (P ≤ 0.001). • As expected, DSS in the higher-LND group worsened with each 5% increase in LND threshold: patients with LND > 35% had a 5-year DSS rate of 4%. • Using our data as a tool, multiple cut-offs can be employed to categorize patients into various risk groups with different risk. For example, patients with LND ≤ 10% have an estimated 5-year DSS rate of 61.9%, whereas patients with LND > 15% have an estimated 5-year DSS rate of 19.2%. CONCLUSIONS • Patients with node-positive bladder cancer have poor outcomes, and survival varies widely according to LND. • Categorical LND should be used to risk-stratify patients for counselling regarding prognosis. • Furthermore, categorical LND should be used as a tool for designing and reporting on clinical trials of adjuvant therapies.

Background There are limited data regarding the differences in clinical presentation and outcome of liposarcomas between adult and pediatric patients. The role of adjuvant radiotherapy in the treatment of childhood liposarcoma is unclear.

Purpose Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy. Patients and Methods Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT. Results Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group. Conclusion Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.

Robot assisted radical cystectomy outcomes show feasibility and potential benefits for patient recovery. However, it is difficult to judge the completeness of extended robot assisted vs open pelvic lymph node dissection using only the lymph node count and template description. We performed a prospective protocol in which radical cystectomy and pelvic lymph node dissection done in robot assisted fashion were followed by second look open pelvic lymph node dissection. Our primary objective was to determine the fraction of lymph nodes yielded by robot assisted pelvic lymph node dissection.Patients with pure transitional cell carcinoma and no locally advanced features were selected for robot assisted radical cystectomy. A team of 2 urological oncologists performed radical cystectomy and pelvic lymph node dissection in robot assisted fashion, followed by second look open pelvic lymph node dissection. Lymph nodes from robot assisted dissection were submitted in up to 8 separate specimens by anatomical location. Any additional specimens retrieved at open dissection were submitted separately.The protocol was completed in 11 patients from October 2007 to June 2009. The median yield of robot assisted and second look open pelvic lymph node dissection was 43 (range 19 to 63) and 4 (range 0 to 8), respectively, for an overall robot assisted yield of 93%. Of second look open pelvic lymph node dissections 67% were clear of residual tissue, 13% had tissue without lymph nodes and 20% had 1 or more lymph nodes. Median operative time for robot assisted pelvic lymph node dissection was 117 minutes. Concurrently open radical cystectomy without required multiple lymph node specimen submission yielded a median 24 nodes.Our data showing a robot assisted pelvic lymph node dissection yield of 93% of that of open surgery should allay concern that the robot assisted technique limits the completeness of pelvic lymph node dissection.

BACKGROUND: Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes. METHODS: Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein. RESULTS: The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings. CONCLUSIONS: Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy. Cancer 2011. © 2010 American Cancer Society.

Introduction: Clinical staging of patients with advanced cervical cancer according to International Federation of Gynecology and Obstetrics (FIGO) is often inaccurate. The purpose of this study is to determine the feasibility of performing an extraperitoneal laparoscopic lymphadenectomy in patients with stage IB2-IVA cervical carcinoma. Also, this study will evaluate the rate of histologically-confirmed para-aortic lymph node metastases relative to preoperative regional imaging via positron emission tomography/computed tomography (PET/CT). Finally, we demonstrate the ability to effectively train an inexperienced surgeon to perform extraperitoneal laparoscopic lymphadenectomy within the predefined feasibility parameters of an experienced surgeon. Patients and Methods: Patients with a biopsy-proven stage IB2 to IVA cervical carcinoma who were candidates for treatment with radiation therapy and concurrent chemotherapy were eligible for inclusion. All patients underwent preoperative PET/CT and subsequent extraperitoneal para-aortic lymphadenectomy. The initial phase of the study enrolled 10 patients to determine the feasibility of the procedure. A second cohort of up to 20 patients was prospectively evaluated upon which data were gathered determining successful surgical evaluation and associated complication rates. A third cohort of 30 patients was enrolled from which 10 were to be performed by a second surgeon with no baseline facility with the procedure. The same feasibility criterion was leveraged against this physician. Data on this surgeon’s learning experience was gathered and recorded. Conclusion: The accumulated data from this trial awaits presentation at the 2010 Annual Meeting of the Society of Gynecologic Oncologists. However, of equal importance is the formulation of an objective measurement of the acquisition of more advanced surgical skills among experienced surgeons.

Object Despite a favorable outcome for most patients with WHO Grade I meningiomas, a subset of these patients will have recurrent or progressive disease that advances to a higher grade and requires increasingly aggressive therapy. The goal of this study was to identify clinical characteristics associated with the recurrence of benign meningiomas and their acceleration to atypical and malignant histological types. Methods Records of 216 patients with WHO Grade I, II, or III meningioma that were initially treated between 1965 and 2001 were retrospectively reviewed. Median follow-up was 7.2 years. Results Patients with non–skull base cranial meningiomas (82 of 105 [78%]) were more likely to have undergone a gross-total resection than patients with skull base meningiomas (32 of 78 [41%]; p < 0.001). Consequently, patients with Grade I non–skull base cranial meningiomas had better 5-year recurrence-free survival (69%) than patients with Grade I skull base meningiomas (56%) or Grade II or III tumors at any site (50%; p = 0.005). Unexpectedly, patients with non–skull base tumors who experienced a recurrence (8 of 22 [36%]) were more likely than patients with skull base tumors (1 of 19 [5%]) to have a higher grade tumor at recurrence (p = 0.024). Furthermore, the median MIB-1 labeling index of Grade I non–skull base cranial meningiomas (2.60%) was significantly higher than that of Grade I skull base tumors (1.35%; p = 0.016). Conclusions Cranial meningiomas that occur outside of the skull base are more likely to have a higher MIB-1 labeling index and recur with a higher grade than those within the skull base, suggesting that non–skull base cranial tumors may have a more aggressive biology than skull base tumors.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To measure the time and subjective quality of individual steps of robot-assisted radical prostatectomy (RARP), as RARP performed by trainees has recently become the most common technique of RP in the USA, and although outcomes from expert surgeons are reported, limited data are available to document training experiences. PATIENTS AND METHODS The patients studied were from a prospective cohort of 178 participants (124 with training data). Transperitoneal RARP was performed by one faculty surgeon and one assistant from a rotation of four urological oncology fellows and three residents. RARP was divided into 11 steps, and staff times were recorded for each step. Trainee times and quality scores were recorded for each step, the later defined as grade A equal to staff (A+, no verbal coaching); B, minor corrections; and C, major corrections. Short-term outcomes were recorded to assess the safety of the training. RESULTS The mean (range) console time/case of trainees was 40 (10–123) min. The median console time for a complete case by faculty and by trainees (pooled group) was 128 and 231 min, respectively, an increase in 81%. Individual trainee-performed steps increased in time (compared to staff) by a median range of 50–177%, and the incidence of quality grades

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder. PATIENTS AND METHODS We retrospectively reviewed the records of patients treated with RC and orthotopic urinary diversion between January 1980 and July 2004. RESULTS In all, 260 patients underwent RC with a Studer or Hautmann orthotopic urinary diversion; the median (range) follow-up was 5.1 (0–15.6) years. Six patients (2.3%) developed local recurrence of urothelial cancer (UC) within the urethra after this treatment. The median (range) time to presentation with recurrence after RC was 2.4 (0.7–3.6) years for pT1-4 UC. Recurrences were treated with various methods, including transurethral resection, urethrectomy with conversion of neobladder to continent catheterizable diversion, and chemotherapy. At the last follow-up, four of these six patients were alive without disease, one was alive with disease, and one had died from disease. CONCLUSIONS In our experience, local recurrences involving the urethra are infrequent. Complete surgical excision can provide a good outcome. Neoadjuvant chemotherapy should be considered for recurrences with adverse clinicopathological features.

We assessed the value of lymph node density for predicting disease specific survival after lymphadenectomy for penile cancer.Data were collected retrospectively in 75 and prospectively in 88 consecutive patients with squamous cell carcinoma of the penis treated at M. D. Anderson Cancer Center between 1979 and 2007. We identified 45 patients with penile cancer and nodal metastasis who underwent lymphadenectomy with curative intent. Lymph node density was analyzed as a categorical variable by grouping patients into 2 or 3 categories based on equal percents. We explored the prognostic value of lymph node density for predicting disease specific survival in this cohort.Median followup was 23.7 months in all patients. By the time of analysis 22 patients had died, including 18 (82%) of penile cancer and 4 (18%) of other causes. Median lymph node density in patients alive or dead of other causes was 3.4% (IQR 2.9-5.9) compared to 43.3% (IQR 15.6-80) in those dead of disease (p0.001). Median lymph node density in all patients was 6.7%. Estimated 5-year disease specific survival in patients with lymph node density 6.7% or less was significantly better than that in patients with lymph node density greater than 6.7% (91.2%, 95% CI 53.9-98.8 vs 23.3%, 95% CI 7.0-45.1, p0.001). In models comparing lymph node density to known prognostic features lymph node density remained statistically significant, while the other factors were no longer statistically associated with disease specific survival.Lymph node density proved to be a significantly better prognosticator of disease specific survival than the current TNM nodal staging system in patients with penile cancer and nodal involvement. Further independent validation is required to determine the clinical usefulness of lymph node density in this patient population.

The purpose of this study was to evaluate the impact of increasing the magnesium (Mg(2+)) supplementation in the pre- and posthydration of patients receiving cisplatin plus radiation (CisXRT) to prevent chemotherapy-induced hypomagnesemia (CIH) events.The study was conducted on newly diagnosed cervical cancer patients receiving CisXRT. The first prospective intervention to prevent CIH was to increase the pre- and posthydration Mg(2+) from 1 to 2 g. After completion of the first intervention, the analysis demonstrated the persistent occurrence of CIH on cycle 3, and later, a second intervention was implemented to increase Mg(2+) to 3 g in the pre- and posthydration. Patients that failed to complete at least five cycles or received cisplatin in combination with another chemotherapy regimen were excluded from the study. Baseline group included 70 patients that had received CisXRT prior to any changes in magnesium supplementation.There were 62.8% (44/70) and 32.6% (22/70) of patients with episodes of CIH in the baseline and first intervention groups, respectively (P = 0.007). In the second intervention group, a 49.6% decrease in the total number of episodes compared to control group was observed. Patients in the second intervention group showed a 100% improvement incidence of persistent CIH over the two other cohorts (P = 0.001).The increase of Mg(2+) to 2 g for the initial two cycles and then to 3 g with the third cycle of CisXRT therapy prevented episodes of CIH and decreased associated treatment delays.

Objectives Persistent nodal disease in the surgical specimen (pN+) after preoperative chemotherapy for urothelial carcinoma is associated with a poor prognosis. To improve our understanding regarding the outcomes of such patients, we performed a retrospective review of our experience. Methods From 1993 to 2003, 857 patients underwent radical cystectomy for urothelial carcinoma of the bladder, and 150 were found to have pN+ disease. Of these 150 patients, 37 had pN+ disease despite preoperative chemotherapy and formed the basis of this report. The survival data were analyzed using the Kaplan-Meier method and Cox regression analysis. Results The median patient age was 66 years (range 39-85), and the median follow-up was 50 months (range 13.0-58.7). The clinical stage at the initiation of preoperative chemotherapy was cT2 with lymphovascular invasion in 7, cT3b in 6, cT4a in 4, cT4b in 2, and cN+ in 18. The 2-year overall, disease-specific, and recurrence-free survival rate was 20%, 29.2%, and 13.5%, respectively. Of the 37 patients, 11 (30%) received adjuvant chemotherapy after surgery, most (73%) were platinum-based regimens. On Kaplan-Meier analysis, adjuvant chemotherapy was associated with improved recurrence-free and disease-specific survival. On multivariate analysis, surgical margin status, sex, and histologic type were significantly associated with overall survival, and the histologic type and use of adjuvant chemotherapy were significantly associated with recurrence-free survival. Conclusions Patients with persistent nodal disease despite preoperative chemotherapy have a poor prognosis. A cohort of such patients might do well with adjuvant chemotherapy. The lymph node density and pT category were not prognostic in patients with nodal metastasis after preoperative chemotherapy.

BACKGROUND. Nonbilharzial squamous cell carcinoma (SCC) of the bladder is a rare entity in the Western hemisphere. To further understanding of its natural history, a contemporary experience with management and outcome of this disease was reviewed. METHODS. Between 1988 and 2003, 27 patients with pure SCC were treated at the center. Charts were reviewed to assess impact of therapy on survival and patterns of recurrence in those that died of disease. RESULTS. The 2-year overall survival and recurrence-free survival (RFS) rates were 47.6% and 32.8%, respectively, with a median follow-up of 15.3 months in survivors. Eight patients received initial chemotherapy and/or radiation therapy with the intent of performing surgical consolidation. In 5 of these patients surgical consolidation was not performed due to rapid progression of disease and death. Of the 3 patients who were treated with neoadjuvant therapy (1 with chemotherapy, 1 with radiation, and 1 with chemoradiation) and had surgical consolidation, 2 (67%) were downstaged at cystectomy and remain disease-free. In 10 of 20 patients who underwent radical cystectomy the disease recurred after a median duration of 5.1 months and 7 died: 3 of local recurrence, 1 of distant recurrence, and 3 of both. History of superficial transitional cell carcinoma that differentiated into pure SCC (P 5 .035; hazards ratio [HR] of 3.73) and treatment by radical cystectomy (P 5 .002; HR of 0.19) were associated with RFS. CONCLUSIONS. In select patients with resectable disease, radical cystectomy remains the mainstay of therapy for pure SCC of the bladder. Locoregional recurrence is the primary cause of death in the majority of patients. The role for neoadjuvant therapy is unclear. Cancer 2007;110:764–9. � 2007 American Cancer Society.