Survival and patterns of relapse in patients with oral tongue cancer.

PURPOSE: To evaluate the survival and patterns of relapse for patients with squamous cell carcinoma (SCC) of the oral tongue. PATIENTS AND METHODS: Between 1999 and 2007, 50 patients with SCC of the oral tongue were treated at the University of Colorado Denver. Of the 50 patients, 38 had newly diagnosed SCC of the oral tongue (13 with stage I-II and 25 with stage III-IV disease), and 12 presented with locally recurrent SCC. Of the 50 patients, 49 were treated with initial surgery and 1 with definitive chemoradiotherapy. Adjuvant radiotherapy or chemoradiotherapy was administered to 42 patients after surgery. Of the 13 patients with newly diagnosed stage I-II disease, 7 did not receive adjuvant therapy. The actuarial locoregional control, freedom from distant relapse, and survival were determined using the Kaplan-Meier method, and comparisons were made using the log-rank test. RESULTS: The median follow-up was 29 months (range 4 to 95) for living patients. The 2-year locoregional control and freedom from distant relapse rate was 58% and 83%, respectively. Locoregional control was particularly low among patients with stage I-II disease, for whom the 2-year locoregional control rate was only 35%. The median survival time and 2-year survival rate for all patients was 42 months and 65%, respectively. The 2-year survival rate for patients with stage I-II oral tongue cancer was 77% compared with 52% for patients with stage III-IV disease (P = .04). CONCLUSIONS: Despite aggressive therapy, patients with SCC of the oral tongue have a low rate of local tumor control and survival, particularly among those with stage I-II disease. These patients should be considered for inclusion in clinical trials evaluating novel postoperative therapies.

Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? A patterns-of-failure analysis.

INTRODUCTION: The pattern of failure (POF) after first-line systemic therapy in advanced non-small cell lung cancer (NSCLC) is unknown. We evaluate the POF in this setting to estimate the potential value of consolidative stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: The records of consecutive NSCLC patients presenting to the University of Colorado, Denver (UCD) between January 2005 and June 2008 were reviewed. Patients with measurable advanced stage NSCLC who received first-line systemic therapy and follow-up at UCD were eligible. In these patients, sites of disease at maximal response were evaluated for theoretical SBRT eligibility, based on institutional criteria. All patients were followed to extracranial progression. The POF was categorized as local (L) for lesions known prior to treatment or distant (D) for new lesions. RESULTS: Among 387 consecutive lung cancer patients (all stages), 64 met the eligibility criteria and 34 were SBRT-eligible. Among all eligible patients, first extra-cranial progression was L-only in 64%, D-only in 9% and L + D in 27%. Among SBRT-eligible patients, POF was L-only in 68%, D-only in 14% and L + D in 18%. In SBRT-eligible patients, time to first progression was 3.0 months in those with L-only failure versus 5.7 month in those with any D failure (HR 0.44; 95% CI 0.22-0.90). CONCLUSIONS: The predominant POF in patients with advanced NSCLC after first-line systemic therapy is local-only. The current analysis suggests that SBRT could improve time to progression in a substantial proportion of patients. The estimated increase in time to progression using this approach would be approximately 3 months.

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PURPOSE: Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. METHODS AND MATERIALS: Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. RESULTS: Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. CONCLUSIONS: IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

Improved survival in patients with Stage III-IV Head and neck cancer treated with radiotherapy as primary local treatment modality.

PURPOSE: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. METHODS AND MATERIALS: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. RESULTS: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. CONCLUSIONS: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

Use of external beam radiotherapy is associated with reduced incidence of second primary head and neck cancer: a SEER database analysis.

PURPOSE: Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA). METHODS AND MATERIALS: The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined and compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA. RESULTS: Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91). CONCLUSION: For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.

Accelerated partial-breast intensity-modulated radiotherapy results in improved dose distribution when compared with three-dimensional treatment-planning techniques.

PURPOSE: To compare dose distribution and normal tissue sparing in partial-breast treatment using three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Sixty-three patients with Tis-1N0M0 breast cancer were treated on a Phase II prospective accelerated partial-breast IMRT protocol at two facilities between April 2004 and January 2006. Fifty-six patients had data sets sufficient to adequately contour all structures. These cases were subsequently replanned with 3D-CRT techniques using the same contours, to compare the dose distribution patterns of 3D-CRT vs. IMRT. RESULTS: The average planning target volume (PTV) to ipsilateral breast (IB) ratio was 24% (range, 7-58%). The average volume of IB receiving 25%, 50%, 75%, and 100% of the prescribed dose was 4.0%, 5.0%, 5.5%, and 10.5% less with IMRT than with 3D (p < 0.01). The dose reduction to normal breast was further improved in the subset of patients whose PTV to IB ratio was >25%, and in patients with contoured breast volume <750 cm(3). No difference was detected in delivery to the lumpectomy cavity or clinical target volume. The PTV volume receiving 95% of the dose was higher in the 3D conformal plans (p < 0.01), but no significant difference was observed in the PTV volume receiving 90% (p = 0.17). The irradiated heart and lung volumes were small with both techniques but also favored IMRT. CONCLUSIONS: In T1N0 patients treated with external beam partial-breast radiotherapy, IMRT improves normal tissue sparing in the ipsilateral breast compared with 3DRT, without compromising dose delivery to the lumpectomy cavity and clinical target volume.

High incidence of lung cancer after non-muscle-invasive transitional cell carcinoma of the bladder: implications for screening trials.

PURPOSE: Lung cancer screening trials depend on the selection of a sufficiently high-risk population. Because not all smokers develop cancer, we hypothesize that a history of tobacco-associated malignancy might more reliably predict for subsequent lung cancer. Because patients with early-stage bladder transitional cell carcinoma (TCC) often have a long survival, we considered whether they would constitute a suitable population for a screening study. PATIENTS AND METHODS: Patients with Ta/is/1 N0 M0 TCC of the bladder and no history of previous cancer treated surgically between 1983 and 2002 were studied using the Surveillance, Epidemiology, and End Results (SEER) database. The incidence and cancer-specific mortality of second nonurothelial solid organ cancers was determined. The standardized incidence ratio (SIR) and 15-year actuarial incidences were determined. RESULTS: From 1983 to 2002, 8300 patients meeting the inclusion criteria were entered into the SEER-9 Registry. Among them, the SIR for a second solid organ malignancy was 1.25 (95% CI, 1.18-1.32). The SIR was significantly increased for tumors of the lung (1.71), head and neck (1.32), and prostate (1.28). The 15-year incidence of and mortality from lung cancer were 8.8% and 8.6%, respectively. Among all nonurothelial second malignancies, lung cancers accounted for 32.5% of the incidence and 53.4% of cancer-specific deaths. Moreover, lung cancer accounted for 12.2% of overall deaths in these patients. CONCLUSIONS: Patients with non-muscle-invasive bladder TCC suffer a high incidence of mortality from lung cancer and might constitute a suitable population for a lung screening trial. Other tobacco-related health events might add to smoking history in identifying high-risk populations.

Effect of radiation techniques in treatment of oropharynx cancer.

OBJECTIVES: To compare the toxicity and outcomes of three radiotherapy techniques-three-dimensional conformal (3D-RT), accelerated fractionation with concomitant boost (AFxCB), and intensity modulated radiotherapy (IMRT)-in the combined modality treatment of stage III-IV squamous cell carcinoma (SCC) of the oropharynx. STUDY DESIGN: Retrospective review. METHODS: Between 1998 and 2007, a total of 87 patients were treated; 23 were treated with 3D-RT, 32 with AFxCB, and 32 with IMRT. Systemic therapy consisted of platinum-based chemotherapy in 81 and anti-epidermal growth factor receptor (anti-EGFR)-targeted therapy in 6 cases. Median radiotherapy doses were 70Gy with 3D-RT, 72Gy with AFxCB, and 69.3Gy with IMRT. Locoregional control, survival outcomes, and feeding tube (PEG) dependence were compared using log-rank method. The incidence of acute mucositis and skin reaction, and grade > or = 2 xerostomia at 6, 12, and 18 months after radiotherapy was compared using Fisher's exact test. RESULTS: Median follow-up was 24 months (range 3 to 103 months) for living patients. Two-year overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were 77.3%, 69.5%, and 86.4%, respectively. There was a trend toward improvement in LRC in patients treated with IMRT. Acute grade > or = 3 skin and mucosal toxicity were significantly lower with IMRT compared to AFxCB (P < .001). Grade > or = 2 xerostomia was significantly reduced with IMRT compared to AFxCB and 3D-RT (P < .001). There was no difference in the actuarial rate of PEG dependence (P = .96). CONCLUSIONS: Compared to AFxCB and 3D-RT, IMRT confers an improvement in toxicity and appears to have similar efficacy in patients with SCC of the oropharynx.

Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer.

PURPOSE: Recent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited. METHODS AND MATERIALS: This prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P < .0001). The median PFS (95% confidence interval) was 11.2 months (7.6-15.9 months), and the median OS was 28.4 months (14.5-45.8 months). Survival outcomes were not significantly different for patients with brain metastases (P = .87 for PFS; P = .12 for OS) or lymph node involvement (P = .74 for PFS; P = .86 for OS). CONCLUSIONS: For patients with oligometastatic NSCLC, chemotherapy followed by consolidative radiation therapy without maintenance chemotherapy was associated with encouraging long-term outcomes.

The role of PET-CT fusion in head and neck cancer.

The fusion of 18-fluorodeoxyglucose (FDG) positron-emission tomography (PET) with computed tomography (CT) offers both anatomic and physiologic delineation of head and neck cancers. PET-CT is useful in the staging of head and neck carcinomas and may identify unsuspected distant metastasis that may alter treatment. PET-CT may also help in target volume delineation during radiotherapy (RT) treatment planning. Better characterization of the target may improve local control as well as spare normal tissues from RT sequelae.

Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer.

INTRODUCTION: Outcomes data treating patients with oligometastatic (≤ 5 metastases) non-small cell lung carcinoma (NSCLC) with hypofractionated image-guided radiotherapy (HIGRT) are limited. METHODS: Consecutive oligometastatic NSCLC patients were reviewed from a prospective database. Patients were included if all active diseases were treated with HIGRT. Lesions that had received prior radiation or had radiographic/metabolic resolution after chemotherapy were not treated with HIGRT. Local control of all treated lesions, distant control, progression-free survival (PFS), overall survival (OS), and control of individual lesions (LeC) were calculated. RESULTS: Twenty-five patients with median of 2 treated oligometastatic lesions were included. Median follow-up was 14 months. Median age was 66 years. Nineteen patients received systemic therapy before HIGRT and 11 had progressive disease after their most recent systemic therapy before HIGRT. Median OS and PFS were 22.7 and 7.6 months. The 18 months local control, distant control, OS, and PFS were 66.1%, 31.7%, 52.9%, and 28.0%. Greater than two sites treated with HIGRT, nonadenocarcinoma histology, prior systemic therapy, and progression after systemic therapy were associated with worse PFS. Sixty-two individual lesions of median size 2.7 cm were treated. For extracranial lesions, median total and fraction dose were 50 and 5 Gy. Median standard equivalent dose in 2 Gy fractions for extracranial lesions was 64.6 Gy yielding 18 months LeC of 70.7%. Standard equivalent dose ≥64.6 Gy increased LeC (p = 0.04). Two patients experienced grade 3 toxicity. CONCLUSIONS: HIGRT for oligometastatic NSCLC provides durable LeC and may provide long-term PFS in some patients. Future HIGRT studies should optimize patient selection and integration with systemic therapy.

Phase I trial of hypofractionated intensity-modulated radiotherapy with temozolomide chemotherapy for patients with newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the maximal tolerated biologic dose intensification of radiotherapy using fractional dose escalation with temozolomide (TMZ) chemotherapy in patients with newly diagnosed glioblastoma multiforme. METHODS AND MATERIALS: Patients with newly diagnosed glioblastoma multiforme after biopsy or resection and with adequate performance status, bone marrow, and organ function were eligible. The patients underwent postoperative intensity-modulated radiotherapy (IMRT) with concurrent and adjuvant TMZ. All patients received a total dose of 60 Gy to the surgical cavity and residual tumor, with a 5-mm margin. IMRT biologic dose intensification was achieved by escalating from 3 Gy/fraction (Level 1) to 6 Gy/fraction (Level 4) in 1-Gy increments. Concurrent TMZ was given at 75 mg/m(2)/d for 28 consecutive days. Adjuvant TMZ was given at 150-200 mg/m(2)/d for 5 days every 28 days. Dose-limiting toxicity was defined as any Common Terminology Criteria for Adverse Events, version 3, Grade 3-4 nonhematologic toxicity, excluding Grade 3 fatigue, nausea, and vomiting. A standard 3+3 Phase I design was used. RESULTS: A total of 16 patients were accrued (12 men and 4 women, median age, 69 years; range, 34-84. The median Karnofsky performance status was 80 (range, 60-90). Of the 16 patients, 3 each were treated at Levels 1 and 2, 4 at Level 3, and 6 at Level 4. All patients received IMRT and concurrent TMZ according to the protocol, except for 1 patient, who received 14 days of concurrent TMZ. The median number of adjuvant TMZ cycles was 7.5 (range, 0-12). The median survival was 16.2 months (range, 3-33). One patient experienced vision loss in the left eye 7 months after IMRT. Four patients underwent repeat surgery for suspected tumor recurrence 6-12 months after IMRT; 3 had radionecrosis. CONCLUSIONS: The maximal tolerated IMRT fraction size was not reached in our study. Our results have shown that 60 Gy IMRT delivered in 6-Gy fractions within 2 weeks with concurrent and adjuvant TMZ is tolerable in selected patients with a T(1)-weighted enhancing tumor <6 cm.

Favorable prognosis in patients with high-grade glioma with radiation necrosis: the University of Colorado reoperation series.

PURPOSE: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). METHODS AND MATERIALS: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if ≥80% of the specimen was necrotic and as tumor recurrence if ≥20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. RESULTS: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p=0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. CONCLUSIONS: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.

Phase I trial of bortezomib and concurrent external beam radiation in patients with advanced solid malignancies.

PURPOSE: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. METHODS AND MATERIALS: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m(2), 1.3 mg/m(2), and 1.6 mg/m(2)/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade ≥3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for ≥2 weeks. RESULTS: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m(2). One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). CONCLUSIONS: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m(2) is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m(2).

Cardiac mortality in patients with stage I and II diffuse large B-cell lymphoma treated with and without radiation: a surveillance, epidemiology, and end-results analysis.

PURPOSE: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality. METHODS AND MATERIALS: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. RESULTS: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005). CONCLUSIONS: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.

Initial results of a Phase I dose-escalation trial of concurrent and maintenance erlotinib and reirradiation for recurrent and new primary head-and-neck cancer.

PURPOSE: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). METHODS AND MATERIALS: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinib started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. RESULTS: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. CONCLUSIONS: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.