Gynecologic oncology care during the COVID-19 pandemic at three affiliated New York City hospitals.

BACKGROUND: New York City was among the epicenters during the COVID-19 pandemic. Oncologists must balance plausible risks of COVID-19 infection with the recognized consequences of delaying cancer treatment, keeping in mind the capacity of the health care system. We sought to investigate treatment patterns in gynecologic cancer care during the first two months of the COVID-19 pandemic at three affiliated New York City hospitals located in Brooklyn, Manhattan and Queens. METHODS: A prospective registry of patients with active or presumed gynecologic cancers receiving inpatient and/or outpatient care at three affiliated New York City hospitals was maintained between March 1 and April 30, 2020. Clinical and demographic data were abstracted from the electronic medical record with a focus on oncologic treatment. Multivariable logistic regression analysis was explored to evaluate the independent effect of hospital location, race, age, medical comorbidities, cancer status and COVID-19 status on treatment modifications. RESULTS: Among 302 patients with gynecologic cancer, 117 (38.7%) experienced a COVID-19-related treatment modification (delay, change or cancellation) during the first two months of the pandemic in New York. Sixty-four patients (67.4% of those scheduled for surgery) had a COVID-19-related modification in their surgical plan, 45 (21.5% of those scheduled for systemic treatment) a modification in systemic treatment and 12 (18.8% of those scheduled for radiation) a modification in radiation. Nineteen patients (6.3%) had positive COVID-19 testing. On univariate analysis, hospital location in Queens or Brooklyn, age ≤65 years, treatment for a new cancer diagnosis versus recurrence and COVID-19 positivity were associated with treatment modifications. On multivariable logistic regression analysis, hospital location in Queens and COVID-19 positive testing were independently associated with treatment modifications. CONCLUSIONS: More than one third of patients with gynecologic cancer at three affiliated New York City hospitals experienced a treatment delay, change or cancellation during the first two months of the COVID-19 pandemic. Among the three New York City boroughs represented in this study, likelihood of gynecologic oncology treatment modifications correlated with the case burden of COVID-19.

Evaluation of initial setup errors of two immobilization devices for lung stereotactic body radiation therapy (SBRT).

The aim of this study was to investigate the accuracy and efficacy of two commonly used commercial immobilization systems for stereotactic body radiation therapy (SBRT) in lung cancer. This retrospective study assessed the efficacy and setup accuracy of two immobilization systems: the Elekta Body Frame (EBF) and the Civco Body Pro-Lok (CBP) in 80 patients evenly divided for each system. A cone beam CT (CBCT) was used before each treatment fraction for setup correction in both devices. Analyzed shifts were applied for setup correction and CBCT was repeated. If a large shift (>5 mm) occurred in any direction, an additional CBCT was employed for verification after localization. The efficacy of patient setup was analyzed for 105 sessions (48 with the EBF, 57 with the CBP). Result indicates that the CBCT was repeated at the 1st treatment session in 22.5% and 47.5% of the EBF and CBP cases, respectively. The systematic errors {left-right (LR), anterior-posterior (AP), cranio-caudal (CC), and 3D vector shift: (LR2 + AP2 + CC2 )1/2 (mm)}, were {0.5 ± 3.7, 2.3 ± 2.5, 0.7 ± 3.5, 7.1 ± 3.1} mm and {0.4 ± 3.6, 0.7 ± 4.0, 0.0 ± 5.5, 9.2 ± 4.2} mm, and the random setup errors were {5.1, 3.0, 3.5, 3.9} mm and {4.6, 4.8, 5.4, 5.3} mm for the EBF and the CBP, respectively. The 3D vector shift was significantly larger for the CBP (P < 0.01). The setup time was slightly longer for the EBF (EBF: 15.1 min, CBP: 13.7 min), but the difference was not statistically significant. It is concluded that adequate accuracy in SBRT can be achieved with either system if image guidance is used. However, patient comfort could dictate the use of CBP system with slightly reduced accuracy.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus.

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

Acr appropriateness Criteria management of vaginal cancer.

Due to its rarity, treatment guidelines for vaginal cancer are extrapolated from institutional reports and prospective studies of cervical and anal cancer. An expert panel was convened to reach consensus on the selection of imaging and therapeutic modalities. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by the panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four variants were developed to represent clinical scenarios in vaginal cancer management. Group members reached consensus on the appropriateness of the pretreatment evaluation and therapeutic interventions. This article represents the consensus opinion of an expert panel and may be used to inform clinical recommendations in vaginal cancer management.

Evaluation of response after stereotactic body radiotherapy for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence due to hepatitis C. Stereotactic body radiotherapy (SBRT) is a noninvasive, effective therapy in the management of liver malignancies. The authors evaluated radiological response in 26 patients with HCC treated with SBRT at Indiana University. METHODS: Between March 2005 and June 2008, 26 patients with HCC who were not surgical candidates were enrolled in a phase 1 to 2 trial. Eligibility criteria included solitary tumors ≤ 6 cm or up to 3 lesions with sum diameters ≤ 6 cm, and well-compensated cirrhosis. All patients had imaging before, at 1 to 3 months, and every 3 to 6 months after SBRT. RESULTS: Patients received 3 to 5 fractions of SBRT. Median SBRT dose was 42 Gray (Gy) (range: 24-48 Gy). Median follow-up was 13 months. Per Response Evaluation Criteria in Solid Tumors (RECIST), 4 patients had a complete response (CR), 15 had a partial response (PR), and 7 achieved stable disease (SD) at 12 months. One patient with SD experienced progression marginal to the treated area. The overall best response rate (CR + PR) was 73%. In comparison, by European Association for the Study of the Liver (EASL) criteria, 18 of 26 patients had ≥ 50% nonenhancement at 12 months. Thirteen of 18 demonstrated 100% nonenhancement, being > 50% in 5 patients. Kaplan-Meier 1- and 2-year survival estimates were 77% and 60%, respectively. CONCLUSIONS: SBRT is effective therapy for patients with HCC with an overall best response rate (CR + PR) of 73%. Nonenhancement on imaging, a surrogate for ablation, may be a more useful indicator than size reduction in evaluating HCC response to SBRT in the first 6 to 12 months, supporting EASL criteria.

A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: A gynecologic oncology group study.

BACKGROUND: Epithelial growth factor receptor over-expression correlates with poor outcomes in cervical cancer. This study assessed the safety of chemoradiation with cetuximab in the treatment of women with newly diagnosed locally advanced cervical cancer. METHODS: Patients received weekly cisplatin 30 and 40 mg/m(2) [dose level (DL) 1 and 2] and cetuximab 400mg/m(2) loading dose and then 250 mg/m(2) for a total of six weeks with radiotherapy (RT). Patients with nodal metastases received extended field radiation therapy (EFRT). At the maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage, sequential design. RESULTS: In patients receiving pelvic RT, seven were treated at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3 diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8 weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50 days (range, 42-70). In patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis) and 24 in the feasibility phase with eight DLTs [delay in RT >8 weeks due to toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism, mucositis, mucositis with hypokalemia, pain with headache, and platelets with mucositis and headache]. Median EFRT duration was 56 days (range, 36-74). CONCLUSIONS: For patients receiving pelvic RT, cisplatin and cetuximab were feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was not feasible.

ACR Appropriateness Criteria® role of adjuvant therapy in the management of early stage cervical cancer.

OBJECTIVE: The use of adjuvant treatment(s) following initial hysterectomy and retroperitoneal nodal harvesting of patients with clinical stage I and II cervical carcinoma is (are) presently based on the pathological assessment of surgical specimens. This report sought to delineate further the clinical application of potential therapeutic interventions and associated follow-up investigations of this patient cohort. METHODS: The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: From this process, 5 unique clinical variants were developed. These scenarios pertained to options of adjuvant radiation therapy and chemotherapy, methods of delivery of radiotherapy to optimize target volume coverage while simultaneously minimizing radiation exposure of adjacent healthy organs, and recommendations for patient follow-up care. Group members reached consensus of topic ratings in descending order of importance. A risk assessment breakdown was established to highlight the most likely indications for adjuvant treatment(s). CONCLUSION: This assembly by the ACR of physicians involved in the management of patients with early stage cervical cancer was able to describe appropriateness criteria to aid other practitioners in selecting reasonable implementation of postoperative therapies and subsequent surveillance studies. These guidelines await further validation and refinement by both current and future prospectively randomized clinical studies regarding this patient population.

External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. This guideline is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, as consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or before surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies. CONCLUSIONS: The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.

Non-ampullary duodenal adenocarcinoma: factors important for relapse and survival.

BACKGROUND: Duodenal adenocarcinoma (DA) is rare, but potentially curable. Prospective data on treatment outcomes is scarce and large retrospective studies show conflicting results on the impact of radical resection, node-status, and adjuvant therapy. METHODS: In the past 17 years, 30 patients presented with resectable DA. Data on the aforementioned variables were acquired then analyzed for impact on recurrence and survival. RESULTS: Overall-survival rates at 1, 2, and 3 years were 70.0%, 53.3%, and 33.3% respectively. Recurrence-free survival rates at 1, 2, and 3 years were 53.3%, 30.0%, and 26.7%. Overall-survival rates for patients with node-positive disease at 1, 2, and 3 years were 68.8%, 43.8%, 12.5%, and for node-negative 70%, 60%, 60%. Recurrence-free survival in node-positive disease at 1, 2, 3 years was 50%, 12.5%, 12.5%, and for node negative 50%, 50%, and 40%. Median survival from diagnosis was 27.5 months (0.5-226.7 months). Significant predictors of recurrence and survival were nodal-status and AJCC stage (P < 0.001). Adjuvant therapy, surgical-type, pathological tumor-stage, and surgical margins were not significant. CONCLUSION: Nodal-status and overall pathological-stage significantly affect the prognosis for patients with DA, while resection-status and adjuvant therapy may not. The role of adjuvant therapy requires prospective trials for elucidation.

Indiana University experience in the management of vaginal cancer.

PURPOSE: To review our institutional experience in the treatment of primary vaginal cancer and identify predictors for outcome, in particular, recurrence rate. MATERIALS AND METHODS: We retrospectively reviewed the charts of 45 patients identified as having primary squamous cell cancer and adenocarcinoma of the vagina and recorded information regarding both patient and tumor characteristics and treatment modalities. Treatment modalities included surgery and radiation with or without chemotherapy (6 patients), radiation alone (30 patients), and chemoradiation (9 patients). Then, univariate and multivariate analyses were used to identify factors, which predicted for recurrence. Kaplan-Meier survival curves were also generated. RESULTS: The median follow-up time for all surviving patients was 5.8 years (range, 9-146 months). The mean and the median minimum tumor doses were 7300 cGy. The 5-year overall survival rate was 71%, and the 5-year progression-free survival rate was 77%. The 5-year overall survival rates by stage were carcinoma in situ with microinvasion and stage I, 92%; stage II, 82%; and stages III and IVA, 20% (P = 0.0005). The 5-year progression-free survival rates by stage were carcinoma in situ and stage I, 92%; stage II, 88%; and stages III and IVA, 30% (P = 0.00049). Of the factors analyzed, only stage predicted for a statistically significant increased risk for recurrence (P = 2.23E-0.05). CONCLUSIONS: Early-stage vaginal cancer can be successfully managed with radiation therapy with excellent rates of local control and survival. Patients with stages III and IV disease have a very poor outcome, and more aggressive therapies need to be investigated. Given the limited number of patients treated with chemotherapy and radiation, no definitive conclusions can be made regarding the impact of combined therapy in the management of this disease.

Dosimetric impact of gastrointestinal air column in radiation treatment of pancreatic cancer.

OBJECTIVE: Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. METHODS: Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. RESULTS: Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CONCLUSION: CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Current Trends and Controversies.

Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide. Depending on the extent of disease and competing comorbidities for mortality, multiple liver-directed therapy options exist for the treatment of hepatocellular carcinoma. Advancements in radiation oncology have led to the emergence of stereotactic body radiation therapy as a promising liver-directed therapy, which delivers high doses of radiation with a steep dose gradient to maximize local tumor control and minimize radiation-induced treatment toxicity. In this study, we review the current clinical data as well as the unresolved issues and controversies regarding stereotactic body radiation therapy for hepatocellular carcinoma: (1) Is there a radiation dose-response relationship with hepatocellular carcinoma? (2) What are the optimal dosimetric predictors of radiation-induced liver disease, and do they differ for patients with varying liver function? (3) How do we assess treatment response on imaging? (4) How does stereotactic body radiation therapy compare to other liver-directed therapy modalities, including proton beam therapy? Based on the current literature discussed, this review highlights future possible research and clinical directions.

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes.

PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. RESULTS: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non-statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (-25 IU/mL vs -162 IU/mL). CONCLUSIONS: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.

Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience.

OBJECTIVES: Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. METHODS: Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. RESULTS: The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. CONCLUSION: Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications.

Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. The clinical value of many of these molecular markers is now being tested and it may help to refine diagnosis and establish an accurate prognosis. Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. Transtuzumab against Her-2/neu and bevacizumab against VEGF overexpressing carcinomas are among the promising novel treatments. Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.

Long-term safety and efficacy of stereotactic body radiation therapy for hepatic oligometastases.

PURPOSE: To evaluate long-term outcome and toxicity of stereotactic body radiation therapy (SBRT) for hepatic oligometastases from solid tumors. METHODS AND MATERIALS: Eligible patients had 1 to 3 liver metastases, maximum sum diameter 6 cm, without extrahepatic progression. We treated 106 lesions in 81 patients; 67% with colorectal primaries. Median dose was 5400 cGy in 3 to 5 fractions. RESULTS: At median follow-up of 33 months (2.5-70 months), overall local control was 94% (95% confidence interval, not estimable); Kaplan-Meier estimated 96% at 1 year and 91% at 2, 3, and 4 years. Partial/complete response was observed in 69% of lesions with less than 3% progressing. Median survival time was 33.6 months (95% confidence interval, 29.1-38.4); Kaplan-Meier survival estimates at 1, 2, 3, and 4 years were 89.9%, 68.6%, 44.0%, and 28.0%, respectively. Grade 3 or greater liver toxicity was 4.9%. CONCLUSION: SBRT is effective for selected patients with hepatic oligometastases with limited toxicities. A phase 3 trial comparing SBRT with "gold-standard" surgical resection is warranted.

Role of belly board device in the age of intensity modulated radiotherapy for pelvic irradiation.

Small bowel dose often represents a limiting factor for radiation treatment of pelvic malignancies. To reduce small bowel toxicity, a belly board device (BBD) with a prone position is often recommended. Intensity modulated radiotherapy (IMRT) could reduce dose to small bowel based on the desired dose-volume constraints. We investigated the efficacy of BBD in conjunction with IMRT. A total of 11 consecutive patients with the diagnosis of rectal cancer, who were candidates for definitive therapy, were selected. Patients were immobilized with BBD in prone position for simulation and treatment. Supine position computed tomography (CT) data were either acquired at the same time or during a diagnostic scan, and if existed was used. Target volumes (TV) as well as organs at risk (OAR) were delineated in both studies. Three-dimensional conformal treatment (3DCRT) and IMRT plans were made for both scans. Thus for each patient, 4 plans were generated. Statistical analysis was conducted for maximum, minimum, and mean dose to each structure. When comparing the normalized mean Gross TV dose for the different plans, there was no statistical difference found between the planning types. There was a significant difference in small bowel sparing when using prone position on BBD comparing 3DCRT and IMRT plans, favoring IMRT with a 29.6% reduction in dose (p = 0.007). There was also a statistically significant difference in small bowel sparing when comparing supine position IMRT to prone-BBD IMRT favoring prone-BBD IMRT with a reduction of 30.3% (p = 0.002). For rectal cancer when small bowel could be a limiting factor, prone position using BBD along with IMRT provides the best sparing. We conclude that whenever a dose escalation in rectal cancer is desired where small bowel could be limiting factor, IMRT in conjunction with BBD should be selected.

A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases.

PURPOSE: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for liver metastases. METHODS AND MATERIALS: A multicenter Phase I clinical trial was conducted. Eligible patients had one to three liver metastases, tumor diameter <6 cm, and adequate liver function. The first cohort received 36 Gy to the planning target volume (PTV) in three fractions (F). Subsequent cohorts received higher doses up to a chosen maximum of 60 Gy/3F. At least 700 mL of normal liver had to receive a total dose <15 Gy. Dose-limiting toxicity (DLT) included acute Grade 3 liver or intestinal toxicity or any acute Grade 4 toxicity. The MTD was exceeded if 2/6 patients in a cohort experienced DLT. RESULTS: Eighteen patients were enrolled (10 male, 8 female): median age, 55 years (range, 26-83 years); most common primary site, colorectal (6 patients); median aggregate gross tumor volume, 18 ml (range, 3-98 ml). Four patients had multiple tumors. No patient experienced a DLT, and dose was escalated to 60 Gy/3F without reaching MTD. CONCLUSIONS: Biologically potent doses of SBRT are well tolerated in patients with limited liver metastases. Results of this study form the basis for an ongoing Phase II SBRT study of 60 Gy over three fractions for liver metastases.