A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer.

Objectives: Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal cancer, but long-term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods: This trial was an open-label, single-arm, multi-institutional study with a Phase I run-in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2-3 weeks prior to chemoradiation and then, q21 days concurrently with high-dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ-preservation rate (OPR) at 18 months. Results: A total of nine patients were enrolled with a median follow-up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12-month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self-resolved. Conclusion: UCCI-HN-15-02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long-term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow-up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575.Level of evidence: 2b.

Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials.

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.

Enhanced phosphatidylserine-selective cancer therapy with irradiation and SapC-DOPS nanovesicles.

Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner. This was more pronounced if surface PS was initially in the lower range for cancer cells. Radiation also increased the surface PS of tumor cells in subcutaneous xenografts in nude mice. We found an inverse relationship between steady state surface PS level of cancer cell lines and their sensitivity to radiation-induced cell death. In addition, serial irradiation, which selected surviving cells with higher surface PS, also increased resistance to radiation and to some chemotherapeutic drugs, suggesting a PS-dependent mechanism for development of resistance to therapy. On the other hand, fractionated radiation enhanced the effect of a novel anti-cancer, PS-targeting drug, SapC-DOPS, in some cancer cell lines. Our data suggest that we can group cancer cells into cells with low surface PS, which are sensitive to radiation, and high surface PS, which are sensitive to SapC-DOPS. Combination of these interventions may provide a potential new combination therapy.

Development and Validation of Nomograms Predictive of Overall and Progression-Free Survival in Patients With Oropharyngeal Cancer.

Purpose Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Methods To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by calibration plots and the concordance index. Nomograms were externally validated in a cohort of 153 patients with OPSCC randomly assigned to a third trial, NRG Oncology RTOG 9003. Results Both models included age, Zubrod performance status, pack-years, education, p16 status, and T and N stage; the OS model also included anemia and age × pack-years interaction; and the PFS model also included marital status, weight loss, and p16 × Zubrod interaction. Predictions correlated well with observed 2-year and 5-year outcomes. The uncorrected concordance index was 0.76 (95% CI, 0.72 to 0.80) for OS and 0.70 (95% CI, 0.66 to 0.74) for PFS, and bias-corrected indices were similar. In the validation set, OS and PFS models were well calibrated, and OS and PFS were significantly different across tertiles of nomogram scores (log-rank P = .003;< .001). Conclusion The validated nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy.

Relationship between prostate-specific antigen, age, and body mass index in a prostate cancer screening population.

BACKGROUND: Recent studies questioning the benefit of prostate-specific antigen (PSA) screening have increased the need for evaluating factors contributing to variance in levels and their clinical relevance. An inverse relationship between body mass index (BMI) and PSA has been illustrated, however the clinical implications have not been specified. We performed a retrospective review of patients screened through our free screening clinic to delineate any relationship between PSA and BMI in an attempt to understand its possible clinical significance. METHODS: The authors retrospectively reviewed data collected in relation to PSA values and patient characteristics from a community outreach program supplying information and screening for prostate cancer between June of 2003 and August of 2009. RESULTS: Mean BMI of our patient population was 28.7 m/kg(2) (SD 5.4) and our mean PSA value was 1.28 (SD 1.77). Our data indicate a small, but statistically significant decrease in PSA for an increasing BMI with a 0.026 decrease in PSA for every unit increase in BMI. CONCLUSIONS: Our study confirms the previously reported inverse relationship between PSA value and BMI. The significance of this finding and its impact on the value do not seem to indicate a rationale to change the accepted abnormal value in obese patients and should be used in the context of the clinical scenario and other PSA altering factors.

Randomized trial to assess the efficacy of intraoperative steroid use in decreasing acute urinary retention after transperineal radioactive iodine-125 implantation for prostate cancer.

BACKGROUND: Acute urinary retention is a potential complication of brachytherapy, with the literature estimating that 5% to 22% of patients require catheterization within 48 hours after implantation. In theory, postimplantation edema could be reduced by using intraoperative steroids. A prospective trial was conducted randomizing patients to a single intraoperative dose of dexamethasone versus no steroid use. METHODS: In all, 196 evaluable patients who received iodine-125 (I(125)) interstitial brachytherapy alone as definitive treatment for low-to-intermediate risk prostate cancer were randomized to receive either dexamethasone at a dose of 6 mg administered intravenously intraoperatively (Arm A) or no steroids (Arm B). All patients completed the International Prostate Symptom Score before treatment. Patients were contacted by telephone 72 to 96 hours after treatment and the need for catheterization was reported. RESULTS: Between 2003 and 2005, 99 patients received steroids on treatment Arm A and 97 patients were treated according to control Arm B. Treatment arms were balanced with respect to pretreatment characteristics. A total of 3 patients required catheterization (2 in Arm A and 1 in Arm B). The overall rate of catheterization was 1.5%, with no statistically significant difference noted between treatment arms. The 3 patients requiring catheterization had no statistical differences from other patients with respect to pretreatment characteristics, number of seeds/needles used, or postimplantation computed tomography volume of the prostate. CONCLUSIONS: There was no statistically significant difference noted between treatment arms in the current study, leading the authors to conclude that intraoperative dexamethasone did not decrease the rate of catheterization required after brachytherapy. The overall rate of postimplantation catheterization in the current study was 1.5%, which is lower than reported elsewhere in the literature and in a retrospective review from the study institution.

Incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 prostate brachytherapy.

PURPOSE: Hemorrhagic radiation proctitis (HRP) is a potential complication of prostate brachytherapy. We sought to determine the incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 (125I) prostate brachytherapy. PATIENTS AND METHODS: Between 1995 and 2003, 221 consecutive patients were treated at the Barrett Cancer Center with permanent 125I seed implantation for presumed localized adenocarcinoma of the prostate. No patients received EBRT. All cases of HRP were confirmed by colonoscopy. Median follow-up was 52 months. All patients were evaluated for HRP using a 5-grade rectal bleeding scale developed by the Radiation Therapeutic Oncology Group. RESULTS: Thirty-three patients experienced grade>or=1 toxicity at some point after treatment. Twenty patients developed grade 2 toxicity, 9 developed grade 3, and 2 developed grade 4. The median time to onset of symptoms of HRP was 14 months. The incidence of HRP had a bimodal temporal onset, with a peak seen at 4 months and a second larger peak at 16 months. Peak toxicity occurred at 18 months after the onset of rectal bleeding, after which there was a sharp decline in toxicity. CONCLUSION: This study demonstrates tolerable rectal morbidity after transperineal prostate brachytherapy of the prostate. Hemorrhagic radiation proctitis occurring after brachytherapy for prostate cancer is usually self-limiting and frequently resolves without treatment or with minor medical treatment. Patients develop HRP soon after treatment or after a delay in treatment. Symptoms appear to peak 18 months after the onset of HRP.

Interstitial brachytherapy for soft tissue sarcoma: A single institution experience.

PURPOSE: Soft tissue sarcomas (STSs) are an uncommon, histologically diverse group of malignancies, which are primarily treated with surgery. Depending on location and grade, radiation therapy may be used as adjuvant treatment. In this single institution, retrospective series, we examine treatment outcome for STS treated with surgery and adjuvant interstitial brachytherapy (BTX). METHODS AND MATERIALS: Forty-three patients were treated from 1997 to 2005 with adjuvant BTX for primary or recurrent STS. Thirty-four patients were treated for primary and nine for recurrent disease in locations including upper and lower extremity, pelvis, superficial trunk, and retroperitoneum. Twelve patients had low-grade and 31 had high-grade tumors. Most patients had lesions larger than 5 cm. Patients with low-grade tumors received 2500 cGy with BTX, followed by 4500 cGy with external beam radiation therapy (EBRT). High-grade tumors were treated with BTX alone to 4500 cGy if they were considered resectable at the time of diagnosis. For concern about resectability with conservative surgery, patients received 4500 cGy EBRT preoperatively, followed by a 2500 cGy BTX boost. RESULTS: Median followup was 39 months (range, 12-120). Thirty-four patients were known to be alive at last followup. The overall local control rate was 88%; local control was 87% for high-grade tumors and 92% for low-grade tumors. Disease-free survival was 75% overall with 88% free from distant metastases. No patient with low-grade sarcoma developed distant metastasis. Overall survival was 79%. The rate of long-term musculoskeletal or neurologic toxicity >Grade 3 was 7%, with all but a single case occurring in patients treated with EBRT plus BTX. CONCLUSIONS: Adjuvant interstitial BTX seemed to provide acceptable local control with well tolerated treatment in patients with low- and high-grade STS.

A comparison of treatments of squamous cell carcinoma of the base of tongue: surgical resection combined with external radiation therapy, external radiation therapy alone, and external radiation therapy combined with interstitial radiation.

PURPOSE: The outcomes of patients treated at a single institution over a specific time frame using three different therapeutic approaches for cancer of the base of tongue were reviewed. METHODS AND MATERIALS: Between 1992 and 1998, 53 patients were treated with curative intent for base of tongue cancer. Seventeen patients underwent surgical resection with postoperative radiation therapy, 16 patients received definitive external radiation therapy only, and 20 patients were treated with external and interstitial radiation, with neck dissection in 16 of those patients. Local control, survival, and functional status were assessed with each approach. RESULTS: The 5-year actuarial local control and survival for the surgically treated patients were 74% and 44%, respectively. The patients treated with external radiation therapy alone had local control of 28% and 5-year survival of 24%. The patients treated with external and interstitial radiation with neck dissection as indicated had 5-year actuarial local control of 87% and survival of 33%. Survival was not statistically different between the three treatment approaches (p=0.0995) but local control was worse in the definitive external radiation group (p < 0.0001). Speech and swallowing function among the long-term survivors was superior in the definitively irradiated patients compared with the operated patients. CONCLUSION: In this retrospective analysis, survival and local control was lowest in the patients treated with external radiation alone, however, patient selection likely played an important role. Local control was far better with surgical treatment and with external combined with interstitial radiation but survival remains less than 50% with each approach. Surgical treatment was superior for patients with T4 disease. Functional status was higher in the long-term survivors treated nonsurgically.

A Monte Carlo brachytherapy study for dose distribution prediction in an inhomogeneous medium.

The purpose of this study was to present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions. This study was carried out using a Monte Carlo simulation of the dose distribution in homogeneous medium for 3 commonly used brachytherapy seeds. The 3 seeds investigated in this study are iridium-192 (192Ir) iodine-125 (125I), and palladium-103 (103Pd). The computer code was validated by comparing the specific dose rate (Lambda), the radial dose function g(r), and anisotropy function F(r,theta;) for all 3 seeds with the AAPM TG-43 dosimetry formalism and current literature. The 192Ir seed resulted in a dose rate of 1.115 +/- 0.001 cGy-hr(-1)-U(-1), the 125I seed resulted in a dose rate of 0.965 +/- 0.006 cGy/h(-1)/U(-1), and the 103Pd seed resulted in a dose rate of 0.671 +/- 0.002 cGy/h(-1)/U(-1). The results for all 3 seeds are in good agreement with the AAPM TG-43 and current literature. The validated computer code was then applied to a simple inhomogeneous model to determine the effect bone has on dose distribution from an interstitial implant. The inhomogeneous model showed a decrease in dose rate of 2% for the 192Ir, an increase in dose rate of 84% for 125I, and an increase in dose rate of 83% for the 103Pd at the surface of the bone nearest to the source.

Plaque radiotherapy for choroidal and ciliochoroidal melanomas with limited nodular extrascleral extension.

BACKGROUND: Currently available clinical information regarding management of posterior uveal melanomas complicated by nodular extrascleral extension is inadequate to determine the role, if any, for plaque radiotherapy in such patients. METHODS: The authors performed a retrospective descriptive study of eight patients with a choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension who were treated by surgical excision of the extrascleral nodule followed immediately by plaque radiotherapy of the intraocular tumour. The calculated volume of the extrascleral nodule was greater than 1 mm3 but less than 1000 mm3 in all cases, and the intraocular tumour was deemed treatable by plaque radiotherapy in all patients. RESULTS: Four of the eight patients died during available follow-up, three from metastatic melanoma and one from a second cancer. The median length of follow-up for the four surviving patients was 10.1 years. The actuarial 5-year and 10-year all-cause death rates were 37.5% and 53.1% respectively. One of the eight patients experienced local intraocular tumour relapse following plaque therapy and underwent secondary enucleation. None of the patients experienced orbital tumour recurrence or underwent secondary orbital exenteration. INTERPRETATION: Our results coupled with previously published results from another centre suggest that plaque radiotherapy may be an effective local treatment for selected patients with choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension. The fact that none of the patients in this series or in the previously reported series experienced orbital recurrence following plaque radiotherapy or required secondary orbital exenteration suggests that plaque therapy may be better than enucleation alone in terms of these end points. These results should not be extrapolated, of course, to patients with massive extrascleral tumour extension or a choroidal or ciliochoroidal melanoma too large for plaque radiotherapy.

Efficacy of brachytherapy for prostate cancer in African Americans compared with Caucasians.

PURPOSE: To compare the biochemical response to prostate brachytherapy between African Americans and Caucasians in a consecutive series of patients treated at a single institution. METHODS AND MATERIALS: Between July 1995 and October 2001, 173 patients were treated with permanent (125)I seed implantation alone for presumed localized adenocarcinoma of the prostate. Twelve patients were African American and their biochemical response to treatment was compared with the 161 Caucasian patients. The patients were evaluated for biochemical recurrence according to the ASTRO consensus statement and for achieving and maintaining PSA nadirs of < or = 1.0, < or = 0.5, and < or = 0.2. Median pretreatment PSA level was 8 for the African American group and 6 for the Caucasian group. Median Gleason score for each group was 6 and no patients had palpable extraprostatic disease at the time of treatment. RESULTS: None of the African American patients have experienced biochemical recurrence compared with 7.5% of the Caucasian patients (p=0.34). The percentage of African American patients achieving and maintaining a PSA level of < or = 1.0 was 83% compared with 89% for the Caucasian patients (p=0.61). PSA nadir of < or = 0.5 was achieved in 75% of the African American patients and 81% of the Caucasian patients (p=0.52) and 50% of the African American patients experienced PSA levels of < or = 0.2 compared with 59% of the Caucasian patients (p=0.88). CONCLUSION: African American patients with prostate cancer have in general been reported to have worse prognosis compared with Caucasians. This series suggests similar outcome between African American and Caucasian patients treated with brachytherapy for prostate cancer.

Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage possible?

BACKGROUND: Salvage surgery is often the only curative option for recurrent cancer. In patients whose initial tumor is stage T3 or T4, the primary therapy often makes salvage even more difficult. We therefore analyzed the outcome in patients who were originally treated for T3 or T4 squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx and who then had a recurrence and chose to undergo further therapy for cure. PATIENTS AND METHODS: From 1980 to 2000, a total of 940 patients were treated for stage T3 or T4 cancer. Forty-eight patients underwent salvage therapy for recurrence: 24 for primary site recurrence, 20 for regional recurrence, and 4 for locoregional recurrence. RESULTS: The mean time to recurrence was 14.0 months, and the mean survival time was 26.2 months. Among the 28 patients treated for primary site recurrence, the mean time to rerecurrence was 12.6 months, and the mean survival time was 27.3 months. Only 5 of the 28 patients had prolonged survival. The stage of the recurrent disease did not influence outcome. Among the 20 patients treated for neck recurrence, the mean time to recurrence was 14.0 months, and the mean survival time was 25.0 months. Six of the 20 patients had prolonged survival, but none had a recurrence in a previously dissected and irradiated neck. CONCLUSIONS: These results show the limited potential for survival in patients who have a recurrence after treatment for advanced primary site head and neck cancer. Patients who have not undergone all modalities of therapy have the potential for salvage, but even then the chances are limited. Given the morbidity of salvage therapy, and the limited chance for cure, physicians must cautiously counsel patients who are contemplating treatment of recurrent cancer after therapy for advanced disease.

Radiation therapy for recurrent orbital hemangioma.

BACKGROUND: Surgical resection and corticosteroid therapy have traditionally been the preferred methods of treatment for orbital hemangioma. Radiation therapy is not usually indicated because of the potential for ocular complications. With modern radiation techniques, however, patients may experience substantial clinical improvement without significant radiation-induced morbidity. METHODS: A case of unresectable, recurrent orbital hemangioma is described. The clinical presentation, management protocol using radiation therapy, and 5-year follow-up are reviewed. RESULTS: The patient was initially seen with left orbital pain, diplopia, proptosis, and conjunctival edema caused by a recurrent left orbital hemangioma after failed previous surgery. CT scan and angiogram revealed a large, irregular, multilocular mass in the left orbit consistent with hemangioma. The patient was treated with a total of 2000 cGy in 10 treatments. Five-year follow-up revealed a stable, regressed hemangioma with no radiation complications. CONCLUSIONS: Radiation therapy may be used if appropriately indicated for function-threatening orbital hemangioma.

Therapeutic decision making in stages III and IV head and neck squamous cell carcinoma.

BACKGROUND: The best treatment for advanced head and neck cancer remains unclear. Proponents of various therapeutic regimens continue to debate this issue with inconclusive and frequently biased data and with carefully selected patients in controlled trials to support their approach. To assess the outcome of patients in a real-world situation, we reviewed a prospectively maintained database of patients with head and neck cancer. METHODS: We reviewed data from 591 consecutive patients with stage III or IV squamous cell carcinoma treated at a university medical center from January 1, 1992, through December 31, 2000, and analyzed survival using the Kaplan-Meier method. RESULTS: Overall survival was 48%, 40%, and 33% at 2, 3, and 5 years, respectively. We found a significant death rate due to comorbid conditions. The primary tumor was treated surgically (with or without postoperative radiation) in 363 patients, with survival of 55%, 46%, and 38% at 2, 3, and 5 years, respectively. The tumor was treated primarily with radiation therapy (with or without neck dissection) in 193 patients, with survival of 40%, 33%, and 27% at 2, 3, and 5 years, respectively. Overall survival in the surgical group was better than in the radiation group (P =.005, log-rank chi 2 test). The radiation group was subcategorized into those who underwent radiation because the tumor was so advanced as to be unresectable (n = 86), because they were too unhealthy to undergo radical surgery (n = 23), and because they elected radiation therapy (n = 84). Survival in each of the radiation subgroups at 2, 3, and 5 years was 28%, 20%, and 14%, respectively, in the unresectable group; 34%, 22%, and 11%, respectively, in the unhealthy group; and 57%, 53%, and 46%, respectively, in the elective group. Thus, survival in the elective radiation subgroup exceeded that of the surgical group, although not statistically. We analyzed data regarding T and N stages, age, race, surgical margin status, postoperative radiation therapy, chemotherapy, radiation dose, and tumor site. Multivariate analysis of the surgical group and elective radiation subgroup showed that N stage and age were the strongest predictors of survival and that the method of therapy was not significant. For oropharyngeal cancer, the patients in the elective radiation subgroup did as well as the surgical group. Many patients were noncompliant with portions of therapy, with a resulting reduction in survival. CONCLUSIONS: The data demonstrate the value of analyzing a consecutive series of patients with advanced head and neck cancer. By including patients with comorbidities and those who are noncompliant, we determined a realistic expectation of patient outcomes. By including all patients, the data dramatically show the impact of age, comorbidity, and advanced stage on survival. The survival of patients who underwent elective radiation therapy in combination with neck dissection was similar to that of patients treated with primary tumor surgery. This was particularly true for oropharyngeal tumors. The site and stage-specific data are useful in counseling patients with advanced head and neck cancer regarding treatment choices.

Organ preservation with interstitial radiation for base of tongue cancer.

Management options for squamous cell carcinoma of the base of tongue include surgical resection (often with adjuvant radiation), definitive external radiation and external combined with interstitial radiation. The reported series is a single institution experience with interstitial radiation for base of tongue cancer. Twenty patients were treated definitively with interstitial radiation as a boost to external radiation, and four patients were treated palliatively with interstitial radiation alone for recurrent base of tongue cancers or disease arising in a previously irradiated base of tongue. Patient, tumor, and treatment details were analyzed relative to disease control and posttreatment patient function. The 5-year actuarial local control, locoregional control, distant metastasis-free survival, overall disease-free survival, and actuarial overall survival of the definitively treated patients were 86%, 84%, 57%, 41%, and 30%, respectively. The 5-year actuarial rate of tolerating a normal diet was 86%, and all long-term survivors had normal speech function. Of the four patients treated palliatively with interstitial implant alone for recurrent disease (three patients), or a second primary cancer in a previously irradiated site (one patient), local control was obtained in three and long-term disease-free survival was obtained in one. Interstitial implantation combined with external radiation is associated with a high rate of disease eradication with preservation of speech and swallow function. Interstitial radiation alone can achieve effective palliation.