Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Rational Second-Generation Antiandrogen Use in Prostate Cancer.

The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations. Complete tabular and graphical representation of all available evidence is provided regarding the use and sequencing of second-generation antiandrogens in prostate cancer. In metastatic castration-resistant prostate cancer, evidence suggests prioritization of abiraterone before chemotherapy, chemotherapy after second-generation antiandrogen failure, and postchemotherapy enzalutamide in select patients to maximize agent efficacy and tolerability. We conclude that a rational, optimized sequencing of second-generation antiandrogens with other treatment options is feasible with present data.

Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

PURPOSE: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. PATIENTS AND METHODS: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. RESULTS: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7-CD45RA-) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. CONCLUSIONS: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

INTRODUCTION: Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate. METHODS: Utilizing an institutional database search tool, we queried the electronic medical record to identify patients with SCC or neuroendocrine carcinoma of the prostate who had been treated with atezolizumab and chemotherapy. We recorded patient characteristics, including age, pathology, and disease extent. Treatment characteristics included number of prior treatments, use of concominant androgen deprivation, number of cycles of immunotherapy, and prior systemic therapies (including those for adenocarcinoma of the prostate). Progression free survival (PFS) and overall survival (OS) were the primary outcomes. RESULTS: We identified seven men who received atezolizumab for metastatic prostate cancer with a small cell or neuroendocrine component. In six of the seven patients, the combination of carboplatin, etoposide, and atezolizumab was the first-line of treatment after diagnosis of small cell or neuroendocrine carcinoma. Two of the seven patients had de novo small cell/neuroendocrine pathology, while the other five had transformation from a preexisting adenocarcinoma. In the patients who received chemotherapy plus immunotherapy in the first-line setting, at a median follow-up of 6.5 months (range: 1.5-15.1) the median PFS was 3.4 months and median OS was 8.4 months. CONCLUSION: Small cell or neuroendocrine carcinoma of the prostate was associated with poor survival outcomes despite adding immunotherapy (atezolizumab) to chemotherapy (carboplatin and etoposide). To our knowledge, there has been no demonstrable benefit of adding immunotherapy to chemotherapy in this setting.

Chemoimmunotherapy after progression on single-agent pembrolizumab for metastatic urothelial carcinoma: a case series.

Those with metastatic urothelial carcinoma generally respond more poorly to chemotherapy after they have progression on a checkpoint inhibitor (CPI). There is interest in combining CPIs with conventional cytotoxic chemotherapies as a strategy to exploit the efficacy and immunomodulatory effects of chemotherapy. We conducted a single institution, retrospective analysis including all patients treated between May 2018 and May 2020 with carboplatin and paclitaxel, concurrently or sequential with pembrolizumab, after having progression on a CPI alone. Clinical characteristics, response by RECIST 1.1, progression-free survival, and safety/tolerance of the treatment are reported. Median age was 80 years (64-85). Five patients (100%) had visceral metastases when starting carboplatin and paclitaxel. Chemotherapy was given with concurrent pembrolizumab (four patients) or following pembrolizumab (one patient) and continued until maximum response, significant toxicity, or progression. Two patients subsequently remained on maintenance pembrolizumab. There were four partial responses and one patient with stable disease. All patients on follow-up have progressed with median time to progression of 47 weeks (18-75). Two patients died from disease progression. This case series suggests that the combination of carboplatin, paclitaxel, and pembrolizumab leads to durable freedom from progression in some with metastatic urothelial cancer, who have progressed on a CPI alone. Larger studies of chemoimmunotherapy for metastatic urothelial carcinoma are warranted.

Penile cancer with visceral metastasis and p16/human papillomavirus positivity: An unusual case of long-term survival.

Squamous cell carcinoma (SCC) of the penis is a rare cancer in the industrialized countries, including the United States. Risk factors for these cancers include inflammatory conditions as well as infection with the human papilloma virus (HPV). Treatment modalities are based on TNM staging and may include surgical management or chemoradiation. Patients with local or some regional disease can have a favorable prognosis; however, with extranodal metastasis, survival decreases sharply. Here, we present a case of long-term disease-free survival in a patient with widely metastatic SCC of the penis.

11C-Choline PET Guided Salvage Radiation Therapy for Isolated Pelvic and Paraortic Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Rationale and Early Genitourinary or Gastrointestinal Toxicities.

PURPOSE: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of 11C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy. METHODS AND MATERIALS: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.25 Gy), all in 25 fractions. RT-naïve patients had the prostatic fossa included in the initial treatment volumes followed by a sequential boost (median dose, 68 Gy). GI and GU AEs were reported per Common Terminology Criteria for Adverse Events (version 4.0) with data gathered retrospectively. Differences in maximum GI and GU AEs at baseline, immediately post-RT, and at early (median, 4 months) and late (median, 14 months) follow-up were assessed. RESULTS: Median follow-up was 16 months (interquartile range [IQR], 11-25). Median prostate-specific antigen at time of positive CholPET was 2.3 ng/mL (IQR, 1.3-4.8), with a median of 2 (IQR, 1-4) choline-avid LNs per patient. Most recurrences were within the pelvis (53%) or pelvis + paraortic (40%). Baseline rates of grade 1 to 2 GI AEs were 8.4% compared with 51.9% (4.7% grade 2) of patients post-RT (P < .01). These differences resolved by 4-month (12.2%, P = .65) and 14-month AE assessments (9.1%, P = .87). There was no significant change in grade 1 to 2 GU AEs post-RT (64.1%) relative to baseline (56.0%, P = .21), although differences did arise at 4-month (72.2%, P = .01) and 14-month (74.3%, P = .01) AE assessments. CONCLUSIONS: Salvage CholPET guided nodal RT has acceptably low rates of acute GI and GU AEs and no significant detriment in 14-month GI AEs. These data are of value in counseling patients and designing prospective trials evaluating the oncologic efficacy of this treatment strategy.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

PURPOSE: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. MATERIALS AND METHODS: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. RESULTS: A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. CONCLUSIONS: The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Mediastinal seminoma presenting with superior vena cava syndrome.

We present a rare cause of superior vena cava syndrome (SVC) in a previously healthy male aged 31 years. Malignancy was suspected due to unintentional weight loss and childhood exposure to radioactive fallout from a nuclear facility accident. A very large anterior mediastinal mass was identified and demonstrated to be an extragonadal seminoma. Extragonadal germ cell tumours are rare tumours with a high potential for cardiovascular, pulmonary and vascular sequelae. Studies have documented an increased risk of developing seminoma in patients with radioactive exposure. Chemotherapy was initiated, during which the patient experienced progressive and new symptoms, found to be due to extensive thromboembolic disease, which responded well to anticoagulation. Seventy-two months after completing chemotherapy, without need for surgical management, he remains free of the disease.

Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer.

PURPOSE: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). METHODS AND MATERIALS: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. RESULTS: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). CONCLUSIONS: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection.

Outcomes for Patients with Clinical Lymphadenopathy Treated with Radical Prostatectomy.

UNLABELLED: Clinical lymphadenopathy (cN+) from prostate cancer (PCa) identified on imaging remains a contraindication to radical prostatectomy (RP) according to guidelines. We tested the hypothesis that there would be no difference in survival between patients with and without cN+ on preoperative imaging who underwent RP and pelvic lymph node dissection with detection of pelvic lymph node metastasis (LNM). A total of 302 patients with LNM were retrospectively reviewed (1988-2003) and stratified according to cN status on the basis of preoperative imaging. Univariable and multivariable Cox regression analyses were performed to evaluate cN+ as a predictor of survival. Of the 302 patients, 50 (17%) had cN+; the 252 (83%) patients with negative preoperative imaging comprised the cN0 group. During median follow-up of 17.4 yr, 161 deaths were recorded, 70 of which were from PCa. Among the entire LNM cohort, the number of positive lymph nodes (hazard ratio [HR] 1.10; p=0.02) and pathologic Gleason score 8-10 versus ≤6 (HR 2.37; p=0.04) were significant predictors of cancer-specific mortality (CSM). cN+ was not a significant predictor of CSM (p=0.6). Selected patients with cN+ have similar clinical outcomes to those with normal preoperative imaging in the setting of LNM. PATIENT SUMMARY: Clinical lymph node metastases are not a factor in determining survival after radical prostatectomy and pelvic lymph node dissection in patients with prostate cancer. Thus, the presence of clinical lymph node metastases should not be considered as an absolute contraindication to treatment with curative intent.

Natural History of Clinical Recurrence Patterns of Lymph Node-Positive Prostate Cancer After Radical Prostatectomy.

BACKGROUND: Patients with lymph node (LN)-positive prostate cancer (PCa) at radical prostatectomy (RP) face a high risk of cancer recurrence. Nevertheless, recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature. OBJECTIVE: To analyze a large single-institution series with long-term follow-up to elucidate the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Years 1987-2012 of a prospectively maintained institutional RP registry were queried for men with LN-positive PCa at RP. Clinical recurrences were categorized as local, nodal, skeletal, or visceral. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In addition to descriptive statistics and Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards models were constructed to predict recurrence and to quantify the impact of recurrence patterns on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Data from 1011 men with LN-positive PCa at RP were analyzed with 17.6 yr of median follow-up. The 15-yr clinical recurrence rate was 33% (95% confidence interval [CI], 31-35%) for all patients and 52.2% (95% CI, 47.3-57.1%) for patients with biochemical recurrence. The solitary locations were skeletal (n=94, 55%), nodal (n=59, 34%), local soft tissue (n=29, 17%), and visceral (n=8, 5%). Significant multivariable predictors of recurrence were Gleason score 8-10, number of positive nodes, pathologic Gleason score, and more recent year of surgery. The 15-yr CSM after clinical recurrence was 80%, with a mean overall survival of 30 mo after recurrence. On multivariable analysis, recurrences after 5 yr from RP (hazard ratio [HR]: 0.05), multiple recurrences (HR: 1.97), skeletal (HR: 3.13), and visceral metastases (HR: 7.43) were independently associated with CSM (all p<0.05). CONCLUSIONS: Recurrences after RP for LN-positive PCa are heterogeneous in terms of time from RP, location, and number of concomitant lesions. PATIENT SUMMARY: We found that impact of recurrence patterns on cancer-specific mortality varies significantly and allows these patients to be stratified for purposes of prognostication, follow-up, and therapy.

Long-term Treatment Outcomes for Locally Advanced Esophageal Cancer: A Single-Institution Experience.

OBJECTIVES: To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. METHODS: We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. RESULTS: Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). CONCLUSIONS: Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.

Concurrent chemotherapy and intensity modulated radiation therapy in the treatment of anal cancer: A retrospective review from a large academic center.

PURPOSE: To assess the toxicity and efficacy of intensity modulated radiation therapy (IMRT) combined with chemotherapy in treatment of anal cancer. METHODS AND MATERIALS: We examined the records of 34 consecutive patients who received chemoradiation therapy with IMRT as initial treatment for squamous cell carcinoma of the anus between June 2005 and January 2009. The median radiation dose was 50.4 Gy (range, 48.6-57.6 Gy). Chemotherapy was given concurrently: 5-fluorouracil alone in 1 patient and combination 5-fluorouracil and mitomycin C in all others. Endpoints included local control and survival, as well as toxicity. Acute and late toxicity was scored with the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Twenty-eight patients presented with T1 and T2 disease and 6 with T3 and T4 disease. Fourteen patients had regional nodal metastases. The median age was 59 years (range, 46-85 years). Median follow-up in surviving patients was 22 months. The estimated 2-year survival was 93% (95% confidence interval, 76%-98%). Three patients (9%) had local relapse (estimated 2-year local control, 90%; 95% confidence interval, 74%-97%). One patient had relapse in a regional node. Acute grade 3-4 hematologic toxicity was observed in 20 patients (59%). Other acute grade 3 or grade 4 toxicity included the gastrointestinal tract in 3 patients (9%) and skin in 5 patients (15%). Two patients (6%) had late grade 3 or grade 4 gastrointestinal tract toxicity. CONCLUSIONS: Treatment of anal squamous cell carcinoma with IMRT and chemotherapy is effective and has an acceptable toxicity profile.

"Malignant" perivascular epithelioid cell neoplasm: risk stratification and treatment strategies.

Purpose. Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors characterized by a myomelanocytic phenotype, and PEComas occurring in "nonclassic" anatomic distributions are known as perivascular epithelioid cell tumor not otherwise specified (PEComa-NOS). This review aims to compile and analyze cases of PEComa-NOS in an effort to better define their natural history. Design. We evaluated all 234 cases of PEComa-NOS reported in the English literature, extracting information regarding diagnostic features, treatment approaches, and outcomes. Multivariate analysis of a number of variables evaluable on pathologic review was performed to refine preexisting risk stratification criteria. Outcomes for patients receiving nonsurgical treatment are also reported. Results. Primary tumor size ≥5 cm (P = 0.02) and a high (1/50 HPF) mitotic rate (P < 0.0001) were the only factors significantly associated with recurrence following surgical resection. Cytotoxic chemotherapy and radiation therapy have shown little benefit in treating PEComa-NOS; mTOR inhibition is emerging as a treatment option. Conclusion. Progress has been made in understanding the natural history and molecular biology of PEComa-NOS. This review further clarifies risk of recurrence in this disease, allowing clinicians to better risk stratify patients. Further work should focus on applying this knowledge to making treatment decisions for patients with this disease.

Malignant perivascular epithelioid cell tumor of the uterus.

Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors arising in a wide array of anatomic locations and characterized by a myomelanocytic phenotype. PEComas which occur in non-classic anatomic distributions are known as perivascular epithelioid cell tumor-not otherwise specified (PEComa-NOS), and one of the most common primary sites for PEComa-NOS is the uterus. The risk of aggressive behavior of these tumors has been linked to a number of factors evaluable on pathologic review following initial surgical resection. We report a case of PEComa-NOS of the uterus with multiple high-risk features, including frank vascular invasion, with no evidence of recurrent disease 18 months following initial surgical resection.

Intensity-modulated radiotherapy for squamous cell carcinoma of the anal canal: efficacy of a low daily dose to clinically negative regions.

BACKGROUND: We aimed to assess outcomes of patients with anal cancer who underwent intensity-modulated radiotherapy (IMRT) and received less than 1.80 Gy/day. METHODS: We retrospectively reviewed our experience using a low fractional dose (< 1.80 Gy) of IMRT to elective nodal areas for patients receiving chemoradiotherapy for anal cancer. Three-year freedom from any disease relapse and overall survival were estimated using Kaplan-Meier curves. We documented the daily dose that was delivered to clinically uninvolved regions and to areas of gross disease. Incidence of regional failures in high (≥ 1.80 Gy) and low (< 1.80 Gy) daily dose regions was assessed. RESULTS: Thirty-four consecutive patients (median age, 59 years) received IMRT from June 2005 through January 2009. Median follow-up duration was 22 months. Twenty-eight patients had T1 or T2 disease and 6 had T3 or T4 disease. Fourteen patients had nodal metastases. Median treatment dose was 50.40 Gy (range, 48.60-57.60 Gy) in 25 to 32 fractions. The range of fractional doses to clinically negative volumes was 1.28 to 1.80 Gy. Seventeen patients (50%) received a fractional dose of less than 1.60 Gy, 13 (38%) received less than 1.50 Gy, and 9 (26%) received less than 1.40 Gy to at least a portion of the clinically negative volume. Three-year freedom from relapse was 80%, and 3-year overall survival was 87%. No patient had treatment failure in the clinically negative volume that received a low daily dose. CONCLUSIONS: Our data support using doses between 1.50 and 1.80 Gy/day to clinically uninvolved regions.

Adjuvant chemoradiotherapy for resected pancreas cancer.

The purpose of this article is to review pertinent literature assessing the evidence regarding adjuvant chemoradiotherapy for adenocarcinoma of the pancreas following curative resection. This review looks at randomized controlled studies with the emphasis on adjuvant chemoradiotherapy. In assessing the evidence from the studies reviewed in this article, the trials have been grouped according to the positive or negative results for or against adjuvant treatment. In addition, data from two large, single-institution studies affirming the role for adjuvant chemoradiotherapy has been included. Understanding the evidence from all of the randomized studies is important in shaping current practice recommendations for adjuvant therapy of surgically resected pancreas cancer. Adjuvant chemoradiotherapy following surgery is the current approach at many cancer treatment centers in the United States. In Europe, chemotherapy alone is the preferred adjuvant therapy. However, the type of adjuvant treatment recommended remains controversial due to conflicting study results. The debate will likely continue. Current practice should be based on the weight of evidence available at this time, which is in favor of adjuvant chemotherapy with chemoradiotherapy.

The prognostic value of clinical and pathologic factors in esophageal adenocarcinoma: a mayo cohort of 796 patients with extended follow-up after surgical resection.

OBJECTIVE: To identify and describe clinicopathologic prognostic factors in patients with esophageal adenocarcinoma who underwent surgical resection with curative intent. PATIENTS AND METHODS: The study cohort consisted of 796 patients with adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia who underwent complete tumor resection at Mayo Clinic from January 1, 1980, to December 31, 1997. We reviewed individual patient medical records and abstracted demographic, pathologic, perioperative, and cancer outcome data. Median follow-up for vital status and disease recurrence was 12.8 and 5.8 years, respectively. RESULTS: Univariate analysis revealed the following factors to be statistically associated with worse 5-year disease-specific survival: higher N and T status, higher tumor grade, age older than 76 years, and the presence of extracapsular lymph node extension and signet ring cells. The following factors remained significantly linked with worse 5-year disease-specific survival on multivariate analysis: higher N and T status, grade, and age and the absence of preoperative chemotherapy or radiotherapy. Anatomic location of tumor was not associated with differential prognosis. Lymph node metastases were found in 25 (27%) of 93 T1b tumors, 397 (85%) of 468 T3 tumors, and 22 (67%) of 33 T4a tumors. Disease-specific survival was better in T3-4N0 than in T1bN1-3 carcinomas (hazard ratio, 0.50; 95% confidence interval, 0.28-0.89, adjusted for grade and age; P=.02). CONCLUSION: Our results confirm the importance of T and N status and tumor grade and suggest that age may affect prognosis. In addition, we show that a significant proportion of superficial esophageal adenocarcinomas exhibit regional metastases and have worse prognosis than more invasive nonmetastatic tumors.

A single-institution experience with 491 cases of small bowel adenocarcinoma.

BACKGROUND: The optimal treatment of small bowel adenocarcinoma is unknown. METHODS: The records of 491 patients with small bowel adenocarcinoma diagnosis between 1970 and 2005 were reviewed for patient and tumor characteristics, treatment effects, and survival. RESULTS: The median age at diagnosis was 62 years. The most common tumor locations were the duodenum (57%), jejunum (29%), and ileum (10%). The median overall survival was 20.1 months, with a 5-year overall survival of 26%. Greater age, male sex, higher stage and grade, residual disease after resection, and a lymph node ratio of 50% or greater predicted decreased overall survival in univariate analysis. Age and stage were predictive of survival in multivariate analysis. The overall survival with metastatic disease was poor. Adjuvant therapy was not associated with longer overall survival (P = .44). CONCLUSIONS: The prognosis of patients with small bowel adenocarcinoma is poor. Complete resection provides the only means of cure, and the role for adjuvant therapy remains uncertain.