Late toxicity after intensity-modulated radiation therapy for localized prostate cancer: an exploration of dose-volume histogram parameters to limit genitourinary and gastrointestinal toxicity.

PURPOSE: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. METHODS AND MATERIALS: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V(70)), 65 Gy (V(65)), and 40 Gy (V(40)). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. RESULTS: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V(70) ≤ 10%, V(65) ≤ 20%, and V(40) ≤ 40%; 92% for men with rectal V(70) ≤ 20%, V(65) ≤ 40%, and V(40) ≤ 80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. CONCLUSIONS: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies.

BACKGROUND: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1). CONCLUSIONS: Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

Concurrent chemotherapy and intensity-modulated radiotherapy for organ preservation of locoregionally advanced oral cavity cancer.

OBJECTIVES: To report outcomes of oral cavity cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy (chemoIMRT). METHODS: Between 2001 and 2004, 21 patients with oral cavity squamous cell carcinoma underwent definitive chemoIMRT. Sites included were oral tongue (n = 9), floor of mouth (n = 6), buccal mucosa (n = 3), retromolar trigone (n = 2), and hard palate (n = 1). Most had stage III-IV disease (n = 20). The most common regimen was 5 days infusional 5-fluorouracil (600 mg/m(2)/d × 5 days), hydroxyurea (500 mg, PO BID), and 1.5 Gy twice-daily irradiation to 72 to 75 Gy. RESULTS: The median follow-up for surviving patients was 60 months. Treatment failure occurred as follows: local-1, regional-1, and distant metastases-2. The 2- and 5-year estimates of locoregional progression-free survival, disease-free survival, and overall survival were 90% and 90%, 71% and 71%, and 76% and 76%, respectively. Late complications included osteoradionecrosis (3 patients, 14%). CONCLUSIONS: Concurrent chemoIMRT results in promising locoregional control for oral cavity squamous cell carcinomas with acceptable toxicity.

Chemoreirradiation for recurrent salivary gland malignancies.

BACKGROUND AND PURPOSE: To report our experience in treating recurrent salivary gland malignancies using concurrent chemotherapy and reirradiation. MATERIALS AND METHODS: Between 1986 and 2007, 14 patients with locoregionally recurrent salivary gland cancer underwent maximal surgical resection followed by adjuvant 5-fluorouracil and hydroxyurea-based chemotherapy concurrently with 1.5Gy twice daily or 2Gy daily reirradiation. Each cycle consisted of chemoreirradiation for 5 consecutive days followed by a 9-day break. The median reirradiation dose was 66Gy (R 30-72Gy) after a mean radiation treatment interval of 48 months. RESULTS: The median follow-up for all patients was 18 months (R 2-125 months) and 41 months for survivors. The parotid gland (n=6) and minor salivary glands (n=6) were involved more commonly than the submandibular gland (n=2). Locoregional control at 1 and 3years was 72.2% and 51.6%, respectively. Actuarial overall survival at 3 and 5 years was 35.7% and 26.8%, respectively. Tracheostomies and feeding tubes were placed in 2 and 8 patients, respectively. Six patients had feeding tubes at last follow-up or death. CONCLUSIONS: Concurrent chemotherapy and reirradiation for recurrent salivary malignancies result in promising locoregional control for patients with recurrent salivary gland malignancies.

Chemoradiotherapy for locoregionally advanced squamous cell carcinoma of the base of tongue.

BACKGROUND: Our aim was to report the outcomes of base of tongue cancers treated with chemoradiotherapy. METHODS: Between 1990 and 2004, 127 patients with stage III or IV base of tongue cancer were treated with chemoradiotherapy on protocol. Indications included nodal involvement, T3/T4 tumors, positive margins, those patients refusing surgery, or were medically inoperable. The most common regimen was paclitaxel (100 mg/m2 on day 1), infusional 5-fluorouracil (600 mg/m2/day × 5 days), hydroxyurea (500 mg prescribed orally [PO] 2 × daily [BID]), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 51 months. The median dose to gross tumor was 72.5 Gy (range, 40-75.5 Gy). Five-year locoregional progression-free survival, overall survival, and disease-free survival was 87.0%, 58.2%, and 46.0%, respectively. CONCLUSION: Concurrent chemoradiotherapy results in promising locoregional control for base of tongue cancer. As distant relapse was common, further investigation of systemic therapy with novel agents may be warranted.

Thermal assembly of a biomimetic mineral/collagen composite.

A strategy is described for exploiting temperature driven self-assembly of collagen and thermally triggered liposome mineralization to form a mineralized collagen composite from an injectable precursor fluid. Optical density and rheological experiments demonstrated the formation of a collagen gel when acid-soluble type I collagen solutions (1-7 mg/ml) were heated to 24-30 degrees C. Scanning calorimetry experiments demonstrated that mixtures of calcium- and phosphate-loaded liposomes composed of dipalmitoylphosphatidylcholine (90 mol%) and dimyristoylphosphatidylcholine (10 mol%) were stable at room temperature but formed calcium phosphate mineral when heated above 35 degrees C, a consequence of the release of entrapped salts at the lipid chain melting transition. The formation of calcium phosphate mineral induced by triggered release of calcium and phosphate was detected as an endothermic transition (deltaH=6.2+/-1.1 kcal/mol lipid) near the lipid chain melting transition (Tm=37 degrees C). Combining an acid-soluble collagen solution with calcium- and phosphate-loaded liposomes resulted in a liposome/collagen precursor fluid, which when heated from room temperature to 37 degrees C formed a mineralized collagen gel. The dynamic storage modulus of the collagen scaffold increased upon mineralization, and direct nucleation of mineral from the collagen scaffold was detected by electron microscopy.