Shu-Lian Wang

Risk Factors for Pericardial Effusion in Inoperable Esophageal Cancer Patients Treated With Definitive Chemoradiation Therapy

PURPOSE To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT). METHODS AND MATERIALS Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose-volume histogram for the whole heart and pericardium. RESULTS The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0-16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose-volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32-38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE. CONCLUSIONS High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose-volume of the irradiated pericardium and heart.

Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy.

PURPOSE To identify clinical risk factors and dose-volume thresholds for treatment-related pneumonitis (TRP) in patients with non-small cell lung cancer (NSCLC). METHODS AND MATERIALS Data were retrospectively collected from patients with inoperable NSCLC treated with radiotherapy with or without chemotherapy. TRP was graded according to Common Terminology Criteria for Adverse Events, version 3.0, with time to grade > or = 3 TRP calculated from start of radiotherapy. Clinical factors and dose-volume parameters were analyzed for their association with risk of TRP. RESULTS Data from 576 patients (75% with stage III NSCLC) were included in this study. The Kaplan-Meier estimate of the incidence of grade > or = 3 TRP at 12 months was 22%. An analysis of dose-volume parameters identified a threshold dose-volume histogram (DVH) curve defined by V(20) < or = 25%, V(25) < or = 20%, V(35) < or = 15%, and V(50) < or = 10%. Patients with lung DVHs satisfying these constraints had only 2% incidence of grade > or = 3 TRP. Smoking status was the only clinical factor that affected the risk of TRP independent of dosimetric factors. CONCLUSIONS The risk of TRP varied significantly, depending on radiation dose-volume parameters and patient smoking status. Further studies are needed to identify biological basis of smoking effect and methods to reduce the incidence of TRP.

Radiotherapy alone with curative intent in patients with stage I extranodal nasal-type NK/T-cell lymphoma.

PURPOSE This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. METHODS AND MATERIALS The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). RESULTS The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. CONCLUSIONS Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.

Analysis of Radiation Pneumonitis Risk Using a Generalized Lyman Model

PURPOSE To introduce a version of the Lyman normal-tissue complication probability (NTCP) model adapted to incorporate censored time-to-toxicity data and clinical risk factors and to apply the generalized model to analysis of radiation pneumonitis (RP) risk. METHODS AND MATERIALS Medical records and radiation treatment plans were reviewed retrospectively for 576 patients with non-small cell lung cancer treated with radiotherapy. The time to severe (Grade >/=3) RP was computed, with event times censored at last follow-up for patients not experiencing this endpoint. The censored time-to-toxicity data were analyzed using the standard and generalized Lyman models with patient smoking status taken into account. RESULTS The generalized Lyman model with patient smoking status taken into account produced NTCP estimates up to 27 percentage points different from the model based on dose-volume factors alone. The generalized model also predicted that 8% of the expected cases of severe RP were unobserved because of censoring. The estimated volume parameter for lung was not significantly different from n = 1, corresponding to mean lung dose. CONCLUSIONS NTCP models historically have been based solely on dose-volume effects and binary (yes/no) toxicity data. Our results demonstrate that inclusion of nondosimetric risk factors and censored time-to-event data can markedly affect outcome predictions made using NTCP models.

Esophageal Cancer Located at the Neck and Upper Thorax Treated with Concurrent Chemoradiation: A Single-Institution Experience

Background: To characterize the treatment and outcome of patients with cervical and upper thoracic esophageal cancer, the authors retrospectively reviewed the 11-year experience from The University of Texas M. D. Anderson Cancer Center. Methods: Thirty-five patients with M0 cervical or upper thoracic esophageal cancer and treated with concurrent chemoradiotherapy were analyzed. Median radiation dose was 50.4 Gy (range, 24.5–64.8) Gy delivered with 1.8-Gy daily fractions over 5.5 weeks. Chemotherapy was 5-fluorouracil based. Response after treatment was evaluated on the basis of radiography, biopsy, or both. The survival rates were calculated by means of the Kaplan-Meier method. Results: The median follow-up for the surviving patients was 39 months. The actuarial 5-year overall survival (OS), cause-specific survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival rates were 18.6%, 27.6%, 22.4%, 47.7%, and 57.0%, respectively. Patients who received a radiation dose of greater than or equal to 50 Gy had a higher complete response rate than those who received less than 50 Gy (79.2% versus 27.3%; p = 0.003). On multivariate analysis, radiation dose was the only protective factor associated with the rates of OS (p = 0.006), cause-specific survival (p = 0.003), and local relapse-free survival (p = 0.001); tumor stage was the only factor associated with rate of disease-free survival (p = 0.007). Conclusion: Concurrent chemoradiotherapy is an effective treatment modality for patients with cervical and upper thoracic esophageal cancer. The authors’ results suggest that a total radiation dose of 50 to 65 Gy with a concurrent chemotherapy regimen may improve local control and the OS rate in this rare type of esophageal cancer.

Mild Toxicity and Favorable Prognosis of High–Dose and Extended Involved-Field Intensity-Modulated Radiotherapy for Patients With Early-Stage Nasal NK/T-Cell Lymphoma

PURPOSE The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. METHODS AND MATERIALS Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survival were calculated using the Kaplan-Meier method. RESULTS The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. CONCLUSIONS High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.

Failure patterns and clinical implications in early stage nasal natural killer/T-cell lymphoma treated with primary radiotherapy.

This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T‐cell lymphoma treated with primary radiotherapy.

TRIPLE-NEGATIVE OR HER2-POSITIVE STATUS PREDICTS HIGHER RATES OF LOCOREGIONAL RECURRENCE IN NODE-POSITIVE BREAST CANCER PATIENTS AFTER MASTECTOMY

PURPOSE To evaluate the prognostic value of determining estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression in node-positive breast cancer patients treated with mastectomy. METHODS AND MATERIALS The records of 835 node-positive breast cancer patients who had undergone mastectomy between January 2000 and December 2004 were analyzed retrospectively. Of these, 764 patients (91.5%) received chemotherapy; 68 of 398 patients (20.9%) with T1-2N1 disease and 352 of 437 patients (80.5%) with T3-4 or N2-3 disease received postoperative radiotherapy. Patients were classified into four subgroups according to hormone receptor (Rec+ or Rec-) and HER2 expression profiles: Rec-/HER2- (triple negative; n = 141), Rec-/HER2+ (n = 99), Rec+/HER2+ (n = 157), and Rec+/HER2- (n = 438). The endpoints were the duration of locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. RESULTS Patients with triple-negative, Rec-/HER2+, and Rec+/HER2+ expression profiles had a significantly lower 5-year locoregional recurrence-free survival than those with Rec+/HER2- profiles (86.5% vs. 93.6%, p = 0.002). Compared with those with Rec+/HER2+ and Rec+/HER2- profiles, patients with Rec-/HER2- and Rec-/HER2+ profiles had significantly lower 5-year distant metastasis-free survival (69.1% vs. 78.5%, p = 0.000), lower disease-free survival (66.6% vs. 75.6%, p = 0.000), and lower overall survival (71.4% vs. 84.2%, p = 0.000). Triple-negative or Rec-/HER2+ breast cancers had an increased likelihood of relapse and death within the first 3 years after treatment. CONCLUSIONS Triple-negative and HER2-positive profiles are useful markers of prognosis for locoregional recurrence and survival in node-positive breast cancer patients treated with mastectomy.

High-dose and extended-field intensity modulated radiation therapy for early-stage NK/T-cell lymphoma of Waldeyer's ring: dosimetric analysis and clinical outcome.

PURPOSE To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyers ring (WR-NKTCL). METHODS AND MATERIALS Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV50]) and 40 Gy to the negative cervical nodes (PTV40). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS The median mean doses to the PTV50 and PTV40 were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV50 and 0.9% of the PTV40 received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. CONCLUSIONS IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.

Impact of toxicity grade and scoring system on the relationship between mean lung dose and risk of radiation pneumonitis in a large cohort of patients with non-small cell lung cancer.

PURPOSE To compute the risk of radiation pneumonitis (RP) as a function of mean lung dose (MLD), with RP scored using three grading systems and analyzed at four threshold levels of toxicity in a large cohort of patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy (RT). METHODS AND MATERIALS On the basis of medical records and radiographic images, RP was scored retrospectively in 442 patients with NSCLC who had >or=6 months of follow-up after the end of RT. The severity of RP was scored for each patient using the National Cancer Institute (NCI) Common Toxicity Criteria, version 2.0 (CTC2.0); the NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE3.0); and the grading system of the Radiation Therapy Oncology Group (RTOG). For each grading system and for each of four levels of toxicity (Grade >or=1, >or=2, >or=3, >or=4), the Lyman, logistic, and log-logistic normal tissue complication probability (NTCP) models were fitted to the data as functions of MLD. The parameter estimates from the model fits are listed in table form, and the RP risk estimates are presented graphically for the Lyman and log-logistic NTCP models. RESULTS The results presented here illustrate the impact of scoring system and level of toxicity on the relationship between MLD and RP risk. CONCLUSIONS These results facilitate quantitative comparisons between our data and studies of RP risk reported by others, and several examples of such comparisons are provided.