A Phase 1/2 Trial of Brief Androgen Suppression and Stereotactic Radiation Therapy (FASTR) for High-Risk Prostate Cancer.

PURPOSE: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. METHODS AND MATERIALS: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15 patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. RESULTS: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment. One man was not treated owing to discovery of a synchronous primary rectal cancer. Four patients (26%) experienced grade ≥2 toxicity at 6 weeks after treatment. There were 9 of 15 (60%) who experienced grade ≥2 GI or GU toxicity and 4 of 15 (26%) grade ≥3 GI or GU toxicity at 6 months, and 5 of 15 (30%) grade ≥2 GI and GU toxicity at 6 months. A review of the 15 cases did not identify any remedial changes, thus the phase 1 criteria were not met. CONCLUSION: This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual. Treatment factors, such as inclusion of pelvic lymph node radiation therapy, planning constraints, and treatment margins, or patient factors related to the specific frail elderly population may be contributing.

Adenocarcinoma not otherwise specified on dorsum of tongue: case report and literature review.

Primary adenocarcinoma of the oropharynx most often arises from the minor salivary glands, and primary squamous cell carcinoma is more commonly seen arising from the tongue. Few cases of adenocarcinoma not otherwise specified of the tongue have been reported in the literature, and none found on the dorsum of the tongue. Successful treatment strategies have therefore not been defined.We report a case of adenocarcinoma located on the dorsum of the posterior one third of the tongue adjacent to the circumvallate papillae in a woman presenting with globus sensation and mild dysphagia. Treatment consisted of transoral laser excision and postoperative external-beam radiotherapy, resulting in disease-free survival at her 5-year follow-up. The goals of this report are to present a case of adenocarcinoma arising from the minor salivary gland located on the dorsum of the tongue, to discuss previous reports of similar cases, and to suggest that surgery with or without radiotherapy be used as the mainstay of treatment.

Vocal function following radiation for non-laryngeal versus laryngeal tumors of the head and neck.

OBJECTIVE: The larynx may receive high doses of radiation even in the absence of disease. Preliminary investigation has provided evidence that significant voice alterations exist in patients who received radiotherapy (RT) for non-laryngeal tumors of the head and neck. This study evaluates subjective and objective parameters of vocal function in this patient population compared with a control group of patients irradiated for early glottic tumors. STUDY DESIGN: Retrospective cohort study. METHODS: Vocal function in patients irradiated for non-laryngeal and early glottic tumors was assessed in a comprehensive manner and compared. Microanalytical and macroanalytical acoustic analyses, aerodynamic measurements, and videostroboscopy were performed on vowel production data. The Voice Handicap Index was administered for self-assessment of voice quality. All subjects were male, smokers, and greater than 12 months post-RT. RESULTS: Seventeen patients with non-laryngeal tumors and 13 patients with early glottic tumors were evaluated. Microanalytical acoustic parameters were worse for 75% (6 of 8) of the acoustic measures of vowel production in the non-laryngeal group. These include jitter, relative amplitude perturbation, amplitude perturbation quotient, normalized noise energy, pitch amplitude, and spectral flatness ratio. Macroanalytical acoustic analyses revealed no difference in fundamental frequency but numerically smaller phonational frequency range in the non-laryngeal group. All aerodynamic measures, including mean phonation time, mean airflow, and vocal fold diadochokinetic rate, were decreased in the non-laryngeal group. Videostroboscopy demonstrated increased supraglottic activity in the non-laryngeal group. Voice handicap was significantly greater in the non-laryngeal group. CONCLUSIONS: When compared with patients receiving RT for early glottic tumors, there is objective and subjective evidence of vocal dysfunction in patients treated with wide-field RT for non-laryngeal tumors.

Effects of head and neck radiation therapy on vocal function.

OBJECTIVE: Radiotherapy (RT) is used to treat a variety of head and neck malignancies. The larynx may receive high radiation doses even in the absence of disease. The effects of RT on the nondiseased larynx are unknown. This study will evaluate subjective and objective parameters of vocal function in patients treated with RT for nonlaryngeal malignancies. DESIGN: Cross-sectional observational study. METHODS: Videostroboscopic, aerodynamic, and acoustic analyses were performed. Results were compared to age- and gender-matched controls. Self-assessment of voice quality was measured using the Voice Handicap Index. RESULTS: A majority of patients demonstrated increased supraglottal activity (i.e., ventricular fold constriction) during stroboscopic evaluation. Significant differences compared to normative data were found in many aerodynamic and acoustic parameters. A substantial proportion (27%) of patients reported significant voice handicap. Younger patients reported greater handicap, and voice quality was worse with time. CONCLUSIONS: Significant objective and subjective changes in vocal function occur in patients radiated for nonlaryngeal head and neck malignancies. Young patients may have the worst impact, and vocal dysfunction may increase with time. A prospective study of this patient population should include a baseline voice quality assessment.

Hyperbaric oxygen corrects sacral plexopathy due to osteoradionecrosis appearing 15 years after pelvic irradiation.

In 1982, a 55-year-old woman was treated by total cystectomy and adjuvant radiotherapy/chemotherapy for a leiomyosarcoma of the bladder. Fifteen years later she presented with symptoms and signs of sacral plexopathy. Investigations revealed osteoradionecrosis of the sacrum. Hyperbaric oxygen therapy (HBO2) was instituted and progressive resolution of the neurological complaints followed. HBO2 should be considered when managing late-onset sequelae in previously irradiated patients.

Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients.

PURPOSE: A retrospective review of patients with Stage I and II seminoma treated at a regional cancer center was performed to assess the long term efficacy and toxicity associated with post operative radiotherapy. METHODS AND MATERIALS: Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. RESULTS: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. No prognostic factors associated with increased risk of late toxicity or second malignancy were identified, likely a consequence of the small number of these events. CONCLUSION: Survival and toxicity were comparable to that reported in the literature. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma.

Epithelioid leiomyosarcoma of the larynx.

BACKGROUND: Tumors of smooth muscle origin are rare in the upper aerodigestive tract, due to the paucity of smooth muscle in the area. A review of the literature revealed 34 reported cases of leiomyoma, 9 cases of leiomyosarcoma, and only 2 cases of epithelioid leiomyoma arising in the larynx. METHODS: A case report of an epithelioid leiomyosarcoma arising in the right piriform fossa of a 38-year-old man is presented. RESULTS: The tumor was treated with conservative surgical resection and postoperative radiotherapy. There was no evidence of locoregional recurrence 2 years postsurgery, and laryngeal function was preserved. CONCLUSIONS: To our knowledge, this is the third case of a laryngeal epithelioid smooth muscle tumor to be reported in the world literature and the only documentation of an epithelioid leiomyosarcoma arising in the larynx.

Extracapsular axillary node extension in patients receiving adjuvant systemic therapy: an indication for radiotherapy?

PURPOSE: This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. CONCLUSIONS: Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.

Prostate inhibin peptide (PIP) in prostate cancer: a comparative immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.