Prospective evaluation of spinal reirradiation by using stereotactic body radiation therapy: The University of Texas MD Anderson Cancer Center experience

BACKGROUND:

Stereotactic body radiotherapy for previously irradiated, progressive spinal metastases may be a viable option in selected patients. The authors review a prospective series of spinal metastasis patients reirradiated with stereotactic body radiotherapy.

METHODS:

A total of 59 patients with 63 tumors of the spine were reirradiated with stereotactic body radiotherapy between 2003 and 2009. Spinal magnetic resonance imaging was performed both before treatment initiation and at regular follow‐up intervals. Stereotactic body radiotherapy was delivered to a peripheral dose of 30 grays (Gy) in 5 fractions (6 Gy per fraction), or 27 Gy in 3 fractions (9 Gy per fraction). The National Cancer Institute Common Toxicity Criteria 2.0 and McCormick neurological function system were used to evaluate toxicity and neurologic status, respectively.

RESULTS:

Mean follow‐up was 17.6 months. Actuarial 1‐year radiographic local control and overall survival for all patients were both 76%. Of the tumors that progressed after stereotactic body radiotherapy, 13 (81%) of 16 patients had tumors that were within 5 mm of the spinal cord, and 6 of them eventually developed spinal cord compression. Toxicity was most commonly grade 1 or 2 fatigue. Two patients experienced mild to moderate radiation injury (lumbar plexopathy) while remaining independently ambulatory and pain free. Freedom from neurologic deterioration from any cause was 92% at 1 year.

CONCLUSIONS:

Reirradiation for progressive spinal metastases with stereotactic body radiotherapy results in good local control and limited toxicity. Initial surgery should be considered for tumors within 5 mm of the spinal cord. Radiation dose should be tailored for tumors near or invading the psoas muscle secondary to observed risk of lumbar plexopathy. Cancer 2011. © 2011 American Cancer Society.     

Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience

BACKGROUND:

Cushing syndrome (CS) secondary to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome was based on a few case series and individual case reports. Limited data were available about the tumors associated with CS‐EAS in a cancer center setting. In this report, the authors have described their experience with CS‐EAS at The University of Texas MD Anderson Cancer Center to further enhance the current understanding and management of this syndrome.

METHODS:

This was a retrospective review of 43 patients with CS‐EAS who were diagnosed between 1979 and 2009 at The University of Texas MD Anderson Cancer Center.

RESULTS:

Different neuroendocrine tumors were associated with CS‐EAS. Twenty‐one patients (48.9%) had tumors located in the chest cavity, with bronchial carcinoid and small cell lung cancer representing the 2 most common causes. The ACTH source remained occult in 4 patients (9.3%) despite extensive workup. Clinical presentation varied, and the classic features of CS were not evident in some patients. Death occurred in 27 patients (62.8%), and the median overall survival was 32.2 months. Major morbidities included new‐onset or worsening hyperglycemia (77%), symptomatic venous thromboembolism (14%), and infections (23%).

CONCLUSIONS:

In patients with CS‐EAS who attended a comprehensive cancer center, tumors originating in the chest cavity were the leading tumors associated with this syndrome. The authors suspect that CS‐EAS is under reported because of the atypical presentation in some patients. Thus, they suggest careful evaluation of patients with neuroendocrine tumors to avoid missing coexisting CS‐EAS. Cancer 2011;. © 2011 American Cancer Society.     

Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience

Recurrent diffuse intrinsic pontine gliomas (DIPG) are traditionally treated with palliative care since no effective treatments have been described for these tumors. Recently, clinical studies have been emerging, and individualized treatment is attempted more frequently. However, an informative way to compare the treatment outcomes has not been established, and historical control data are missing for recurrent disease. We conducted a retrospective chart review of patients with recurrent DIPG treated between 1998 and 2010. Response progression-free survival and possible influencing factors were evaluated. Thirty-one patients were identified who were treated in 61 treatment attempts using 26 treatment elements in 31 different regimens. The most frequently used drugs were etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic acid (13). Seven patients had repeat radiation therapy to the primary tumor. Response was recorded after 58 treatment attempts and was comprised of 0 treatment attempts with complete responses, 7 with partial responses, 20 with stable diseases, and 31 with progressive diseases The median progression-free survival after treatment start was 0.16 years (2 months) and was found to be correlated to the prior time to progression but not to the number of previous treatment attempts. Repeat radiation resulted in the highest response rates (4/7), and the longest progression-free survival. These data provide a basis to plan future clinical trials for recurrent DIPG. Repeat radiation therapy should be tested in a prospective clinical study.     

Rosai-Dorfman Disease: The MD Anderson Cancer Center Experience

BackgroundRosai-Dorfman disease (RDD) is a rare disorder composed of a proliferation of histiocytes with varied clinical manifestations.Patients and MethodsIn this retrospective observational study, we obtained demographic, clinical, and outcome data from the medical records of 10 adult patients with RDD seen in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center between 1995 and 2015.ResultsPatients had a median age of 56 years (range, 20-81 years) with equal gender distribution. Five patients were initially treated with systemic therapy. Five received cladribine as initial therapy or for relapse. Other therapeutic agents included clofarabine, lenalidomide, and steroids. The overall response rate was 80% in patients receiving cladribine, with a median progression-free survival of 29 months. Surgery, radiotherapy, and observation were also treatment options for localized disease. With a median follow-up of 65 months, none of the patients have died.ConclusionCurrently, there is no standard of care for RDD. Treatment should be personalized for each patient depending on the clinical presentation, course of the disease, and prior treatment history. Purine analogues provide excellent responses; however, surgical resection and observation are also suitable for specific cases.     

Primary chemotherapy in the treatment of breast cancer: the University of Texas M. D. Anderson Cancer Center experience

The use of primary systemic (neoadjuvant) therapy has become widespread in the treatment of patients with locally advanced and operable breast cancer. The utilization of this therapeutic approach provides several advantages. By monitoring changes in the dimension of the tumor, efficacy can be evaluated or assessed in vivo; unnecessary toxicity can be avoided by allowing the physician to discontinue ineffective therapy. Furthermore, downstaging of a tumor through primary therapy may allow for breast-conserving surgery in patients with large operable breast cancer and render inoperable tumors resectable. Also, the use of primary therapy can provide a pathological complete response, which correlates with prolonged periods of remission. Treatment with FAC (5-fluorouracil/doxorubicin/cyclophosphamide) has proven to be effective as neoadjuvant therapy in locally advanced breast cancer in several trials. More recently, the integration of taxanes into primary therapy regimens has been explored with promising results. Studies have suggested that the use of primary therapy, particularly the use of FAC, should perhaps become the standard in patients with locally advanced disease. The history of clinical trials focusing on primary therapy in breast cancer at the M. D. Anderson Cancer Center will be reviewed.     

Small cell carcinoma of the esophagus: the University of Texas M. D. Anderson Cancer Center experience and literature review

BACKGROUND: Small cell carcinoma of the esophagus is a rare disease with aggressive behavior and poor prognosis. Multidrug chemotherapy remains the treatment of choice given the systemic nature of the disease. Radiotherapy has been used concurrently with chemotherapy to enhance local control. The role of surgery in patients with limited disease is controversial. Limited data exist regarding the pathologic response of the tumor to chemoradiotherapy. The goal of the current study was to analyze the outcome of 8 patients treated at the M. D. Anderson Cancer Center, with particular focus on the histologic findings of the resected specimens. METHODS: Patient records were reviewed for demographics, presenting symptoms, diagnostic modalities, disease stage, treatment, and outcome. RESULTS: Two of eight patients had metastatic disease at the time of diagnosis and received combination chemotherapy. Six patients had limited stage disease. Four received combined modality treatment including esophagectomy, and two received radiotherapy only. All four patients who underwent esophagectomy had pure small cell carcinoma histology at diagnosis and received preoperative combination chemotherapy with or without radiotherapy. None of the four patients achieved a pathologic complete remission. Two patients had residual small cell carcinoma; one patient had squamous cell carcinoma and one adenocarcinoma. The median overall survival for the group of patients was 12.5 months (range, 5-57 months). CONCLUSIONS: In selected patients with limited stage disease, surgery with curative intent should be considered as part of multimodality treatment.     

Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients

BACKGROUND: Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience. METHODS: The authors reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at The University of Texas M. D. Anderson Cancer Center. RESULTS: The mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7 patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan-Meier estimates of 5-year and 10-year overall survival (OS) rates were 51% and 24%, respectively. Bladder-sparing therapy with intravesical bacillus Calmette-Guerin therapy was attempted in 27 of 44 patients with nonmuscle-invasive disease; 67% (18 patients) developed disease progression (>or=cT2), including 22% who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (相似文献   

Outcomes in 144 Patients With Colorectal Cancer Treated in a Phase I Clinic: The MD Anderson Cancer Center Experience

BackgroundPatients with advanced colorectal cancer have a poor prognosis once standard therapies fail. This retrospective study presents the characteristics and outcomes in 144 patients treated in phase I clinical trials.MethodsWe retrospectively reviewed the clinical outcomes in 144 consecutive patients with colorectal cancer referred to the phase I clinic at MD Anderson.ResultsMedian age was 60 years (range, 35-86 years). The median number of previous systemic therapies was 4 (range, 1-7). The median PFS with the last line of conventional systemic treatment was 12.3 weeks (95% confidence interval [CI], 11.0-14.4); the median PFS of the best phase I treatment was shorter at 8.1 weeks (95% CI, 7.9-8.7 weeks; log-rank test, P < .0001). In the multivariate analysis that included the RMH score, sex (male vs. female, P = .02; hazard ratio [HR], 1.57), hemoglobin (< 10.5 vs. ≥ 10.5 g/dL; P = .03; HR 1.79), and the RMH score (2-3 vs. 0-1; P < .003; HR, 1.85) were significant predictors of poor survival. Conclusion: The PFS of patients with colorectal cancer in phase I treatment was shorter than it was on their last line of conventional systemic treatment. Multivariate analysis confirmed the value of the RMH score for predicting overall survival in patients with colorectal cancer enrolled in phase I studies.     

Rehabilitation of surgical cancer patients at University of Texas M. D. Anderson Cancer Center

With early detection and treatment, survival rates for many types of cancer have improved. Long term survivors have number of issues, which can include functional deficits, pain, fatigue, lymphedema and altered bowel and bladder function. Simple activities such as mobility and the ability to perform self care can be limited. In addition, re-integration into society with activities such as driving, social interaction and return to work are often problematic. The goal of cancer rehabilitation is to improve quality of life by minimizing disability and handicap caused by cancer and associated treatments. Initial rehabilitation interventions usually occur in an inpatient setting as patients often experience a decline in functional status due to cancer progression and or surgical treatment. Rehabilitation interventions reduce the debility and functional deficits and add to the quality of life for cancer patients undergoing surgical treatments. The rehabilitation team can assist not only with acute decline in functional status but also with re-integration back in society. Both general and specific rehabilitation interventions based on diagnoses are reviewed.     

Combined modality therapy of cT2N0M0 esophageal cancer: the University of Texas M. D. Anderson Cancer Center experience

BACKGROUND:

Treatment strategy for patients with adequately staged cT2N0M0 carcinoma of the thoracic esophagus is currently a subject of debate. This study analyzed the largest series of consecutive cT2N0M0 esophageal cancer patients treated with preoperative chemoradiotherapy.

METHODS:

Data from all patients with cT2N0M0 (assessment included endoscopic ultrasonography and computed tomography of the chest and abdomen) thoracic esophageal cancer who were treated with preoperative chemoradiation between 1997 and 2009 were analyzed. The Cox regression model and Kaplan‐Meier plots were used to analyze the data.

RESULTS:

Data from 49 patients were analyzed. The median follow‐up was 28.46 months. Male sex and adenocarcinoma histology predominated. Pathologic complete response was observed 19 (39%) patients. The 10‐year actuarial overall survival (OS) for adenocarcinoma patients was >60%. In the univariate analysis for OS, squamous histology (P = .006), smoking (P = .015), and alcohol consumption (P = .032) were found to be associated with poor OS. In the univariate analysis for disease‐free survival (DFS), squamous histology (P = .009) and smoking (P = .014) were associated with poor DFS. In the multivariate analysis for OS, smoking was an independent prognosticator (P = .02). In the multivariate analysis for DFS, advanced pathologic stage (P = .05) and lymph node metastases (P = .006) were independent prognosticators. Patients with adenocarcinoma (P = .002) and those with pathologic N0 disease had better OS and DFS. Upward stage migration occurred in only 10% of patients.

CONCLUSIONS:

These data suggest that smoking and alcohol influence the long‐term outcome of patients with cT2N0M0 disease. Adenocarcinoma patients treated with trimodality therapy had an excellent actuarial 10‐year OS and a high rate of pathologic complete response. Trimodality therapy should be prospectively compared with primary surgery in these patients. Cancer 2011. © 2010 American Cancer Society.     

Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson Cancer Center

BACKGROUND: The incidence of testicular carcinoma in the United States has increased significantly over the last two decades. Germ cell tumors form the majority of malignant testicular tumors. With advances in diagnosis and therapeutic approaches, germ cell tumors are now highly sensitive to treatment, providing long-term survival. It has been speculated that the incidence of bilateral germ cell tumors may increase due to the improved survival of patients with unilateral germ cell tumors. In this report, the authors present a study of bilateral germ cell tumors of the testis in men who were treated at The University of Texas M. D. Anderson Cancer Center over a 20-year period with emphasis on their incidence, histologic features, and clinical features. METHODS: Between 1978 and 1999, 2431 patients with testicular germ cell tumors were treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24 patients with bilateral germ cell tumors were identified. Clinical records and all available pathology slides of the tumors were reviewed. RESULTS: The overall incidence of bilateral germ cell tumors in the patients with testicular germ cell tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients) in patients with seminoma and 0.6% (10 of 1655 patients) in patients with nonseminomatous germ cell tumors. Patients with seminoma who were age 相似文献   

Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs

BackgroundCardiac sequelae from oncologic drugs are important in early cancer drug development. Prolongation of the corrected QT interval (QTc) by noncardiac drugs is the most common cause of drug development delays, nonapprovals and postmarketing withdrawals by the US Food and Drug Administration.Patients and methodsWe analyzed 8518 electrocardiograms (ECGs) in 525 consecutive cancer patients enrolled in 22 industry-sponsored phase I clinical trials, starting 1 January 2006.ResultsSeventy-four patients [14%, 95% confidence interval (CI) 11% to 17%] with normal QTc at baseline had QTc intervals above upper limit of normal after treatment initiation; 33 (6%, 95% CI 4% to 9%) had prolonged QTc intervals at baseline, and only one (3%, 95% CI 0% to 16%) worsened after dosing. Seven of 33 patients (21%, 95% CI 9% to 39%) with prolonged baseline QTc had normalization of QTc intervals after dosing. All QTc prolongations were clinically insignificant; study drugs were continued uneventfully. Two of 525 patients (0.4%, 95% CI 0% to 1%) experienced cardiac serious adverse events (myocardial infarction possibly related to drug and unstable atrial flutter related to metastatic disease). Both cardiac events were detected by clinical assessment, not surveillance ECGs.ConclusionFrequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.     

Outcome predictors for 143 patients with superior sulcus tumors treated by multidisciplinary approach at the University of Texas M. D. Anderson Cancer Center

PURPOSE: Superior sulcus tumors (SST) of the lung are uncommon and constitute approximately 3% of non-small cell lung cancer (NSCLC). These tumors cause specific symptoms and signs, and are associated with patterns of failure that differ from those seen for NSCLC tumors in other nonapical locations. Prognostic factors and most effective treatments are controversial. We conducted a retrospective study at The University of Texas M. D. Anderson Cancer Center to identify outcome predictors for patients with SST treated by a multidisciplinary approach. METHODS AND MATERIALS: This retrospective review of 143 patients without distant metastasis at presentation is a continuation of a previous M. D. Anderson study now updated to 1994. In this study, we examine the 5-year survival rate by pretreatment tumor and patient characteristics and by the treatments received. Strict criteria were used to define SST. Actuarial life-table analyses and Cox proportional hazard models were used to compare survival rates. RESULTS: Overall predictors of 5-year survival were weight loss (p < 0.01), supraclavicular fossa (p = 0. 03), or vertebral body (p = 0.05) involvement, stage of the disease (p < 0.01), and surgical treatment (p < 0.01). Five-year survival for patients with Stage IIB disease was 47% compared to 14% for Stage IIIA, and 16% for Stage IIIB. For patients with Stage IIB disease, surgical treatment (p < 0.01) and weight loss (p = 0.01) were significant independent predictors of 5-year survival. Among patients with Stage IIIA disease, the only predictor of survival was Karnofsky performance score (KPS) (p = 0.02). For patients with Stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than that for patients with tumors in the left superior sulcus (p = 0.02). More patients with adenocarcinoma than with squamous cell tumors experienced cerebral metastases within 5 years (p < 0.01). Patients without gross residual disease after surgical resection who received postoperative radiation therapy with total doses of 55 to 64 Gy had a 5-year survival rate of 82% as compared with the 5-year survival rate of 56% in patients who received 50 to 54 Gy. Twenty-three patients survived for longer than 3 years. Of these, 4 patients (17%) received radiation therapy alone or in combination with chemotherapy without surgical resection. The other 19 patients (83%) had resection combined with radiation therapy and/or chemotherapy. CONCLUSIONS: The findings from this study confirm the importance of the new staging system, separating T3 N0 M0 (Stage IIB) from Stage IIIA, since there was a significant difference in the 5-year survival (p < 0.01). Interestingly, there was no significant 5-year survival difference between Stage IIIA (N2) and Stage IIIB (T4 or N3). This study also suggests that surgery is an important component of the multidisciplinary approach to patients with SST if their nodes were negative. Disease that is minimally invading surrounding normal structures can be resected followed by radiation therapy in doses of 55 to 64 Gy. Further investigation of treatment strategies combining high-dose radiation therapy (>/=66 Gy) with chemotherapy is indicated for patients with unresectable and/or node-positive (N2) SST.     

Thymoma Patients Treated in a Phase I Clinic at MD Anderson Cancer Center: Responses to mTOR Inhibitors and Molecular Analyses

BACKGROUND

Thymomas and thymic carcinoma are rare tumors with no approved therapies. Our purpose was to analyze the molecular features and outcomes of patients referred to the Clinical Center for Targeted Therapy (Phase I Clinic).

METHODS

We retrospectively reviewed the medical records of consecutive referred patients with advanced/metastatic thymoma or thymic carcinoma

RESULTS

Twenty-one patients were identified (median age 52 years; 10 women; median number of prior systemic therapies = 2). Six of 10 patients (60%) treated with mTOR inhibitor combination regimens achieved stable disease (SD) ≥12 months or a partial response (PR). For patients treated on mTOR inhibitor regimens (N = 10), median time to treatment failure (TTF) was 11.6 months versus 2.3 months on last conventional regimen prior to referral (p=0.024). Molecular analyses (performed by next generation sequencing in seven patients and single polymerase chain reaction (PCR)-based assays in an additional six patients) showed diverse actionable mutations: PIK3CA (1 of 12 tested; 8%); EGFR (1 of 13; 8%); RET (1 of 7; 14%); and AKT1 (1 of 7; 14%). Of two patients with PIK3CA or AKT1 mutations, one was treated with an mTOR inhibitor-based regimen and achieved 26% regression with a TTF of 17 months.

CONCLUSION

Patients with advanced/metastatic thymoma or thymic carcinoma demonstrated prolonged TTF on mTOR inhibitor-based therapy as compared to prior conventional treatment. Heterogeneity in actionable molecular aberrations was observed, suggesting that multi-assay molecular profiling and individualizing treatment merits investigation.