Neoadjuvant Radiation Therapy with Interdigitated High-Dose LRT for Voluminous High-Grade Soft-Tissue Sarcoma.

Purpose: To report a case of large extremity soft tissue sarcoma (2933 cc), safely treated with a novel approach of interdigitating high-dose LATTICE radiation therapy (LRT) with standard radiation therapy as a neoadjuvant treatment to surgery. Patients and Methods: Four sessions of high-dose LRT were delivered in a weekly interval, interdigitated with standard radiation therapy. The LRT plan consisted of 15 high-dose vertices receiving a dose >12 Gy per session, with 2-3 Gy to the peripheral margin of the tumor. The patient underwent surgical excision 2 months after the new regimen of induction radiation therapy. Results and Discussion: The patient tolerated the radiation therapy regimen well. The post-operative assessment revealed a negative surgical margin and over 95% necrosis of the total tumor volume. The post-surgical wound complication was mitigated by outpatient wound care. Interdigitating multiple sessions of high-dose LATTICE radiation treatments with standard neoadjuvant radiation therapy as a neoadjuvant therapy for soft tissue sarcoma was feasible and did not incur additional toxicity in this clinical case. A phase-I/II trial will be conducted to further evaluate the toxicity and efficacy of the new treatment strategy with the intent to increase the rate of pathologic necrosis, which has been shown to positively correlate with the overall survival.

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT).

The concept of spatially fractionated radiation therapy (SFRT) was conceived over 100 years ago, first in the form of GRID, which has been applied to clinical practice since its early inception and continued to the present even with markedly improved instrumentation in radiation therapy. LATTICE radiation therapy (LRT) was introduced in 2010 as a conceptual 3D extension of GRID therapy with several uniquely different features. Since 2014, when the first patient was treated, over 150 patients with bulky tumors worldwide have received LRT. Through a brief review of the basic principles and the analysis of the collective clinical experience, a set of technical recommendations and guidelines are proposed for the clinical implementation of LRT. It is to be recognized that the current clinical practice of SFRT (GRID or LRT) is still largely based on the heuristic principles. With advancements in basic biological research and the anticipated clinical trials to systemically assess the efficacy and risk, progressively robust optimizations of the technical parameters are essential for the broader application of SFRT in clinical practice.

En bloc resection of lacrimal sac tumors and simultaneous orbital reconstruction: surgical and functional outcomes.

PURPOSE: To describe a surgical technique of en bloc resection of lacrimal sac tumors by the shared expertise of 2 specialists to achieve optimal tumor margin clearance and the simultaneous reconstruction of the bony defect to preserve ocular functions and cosmesis. METHODS: All patients who had resection of malignant nasolacrimal drainage system tumors using the combined technique and posttreatment protocol between 1997 and 2011 were studied in this retrospective, noncomparative, interventional case series. A combined medial maxillectomy and medial orbitotomy for en bloc resection of the lacrimal sac tumor was followed by reconstruction with a tailored contoured titanium mesh to support the globe and eyelid. Disease relapse, disease survival, ocular functions (vision loss, motility, globe dystopia, and diplopia), and cosmesis (medial canthal tendon dystopia and eyelid retraction) were documented. RESULTS: Fourteen patients with malignant lacrimal sac tumors underwent en bloc resection. Postoperative radiation was ultimately administered to 9 patients. All patients but one were alive at last follow up. Tumor recurred locally in 2 patients with a regional recurrence in a third patient. Complications from radiation therapy included skin breakdown over the mesh (9/14 patients) with nasocutaneous fistula, medial canthal tendon dystopia (2/14 patients), and corneal perforation in a patient with recurrent disease. Despite removal of the tear drainage system, only 7 of 14 patients reported epiphora. None of the patients developed diplopia after resection and radiation therapy. CONCLUSIONS: The combined sinus-orbit approach is an effective method of managing lacrimal sac tumors to achieve optimal tumor clearance from the orbit and nasal cavity. Simultaneous reconstruction of the bony defect with a contoured titanium mesh provides a fixation anchor for the medial canthal tendon and globe support and serves as a supporting platform for the lower eyelid and cheek to minimize midface collapse. Postoperative radiation is associated with skin flap breakdown and nasocutaneous fistula formation.

Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer.

INTRODUCTION: In 2003, consolidation docetaxel was a promising concept for unresectable stage IIIA/B nonsmall cell lung cancer (NSCLC). To test the hypothesis that chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel would be feasible and clinically active, we conducted a phase II study. METHODS: Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks. Concurrent radiotherapy was administered more than 7 weeks to a total dose of 63 Gy in 35 fractions. Consolidation docetaxel (75 mg/m) was administered every 3 weeks for 3 doses 4 weeks after chemoradiotherapy. The primary end point was objective response rate by RECIST. RESULTS: Complete responses occurred in 4 patients and partial responses occurred in 14, for an objective response rate of 56.3% (95% confidence interval [CI], 37.7-73.6%). Median progression-free survival was 6.5 months (95% CI, 4.6-13.5); median duration of survival was 14.8 months (95% CI, 6.9-27.3). The most common hematologic toxicity was leukopenia, which were grade 3 or 4 in 16 patients (50%). Radiation pneumonitis (grade >or=2) occurred in 13 of 31 treated patients (42%). CONCLUSIONS: These findings suggested that concurrent chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel is clinically active based on median survival in patients with unresectable stage III NSCLC; however, the 42% incidence of clinical radiation pneumonitis was unexpected and warrants further investigation to determine the mechanism and preventive strategies.

Radiation technique influence on percutaneous endoscopic gastrostomy tube dependence: Comparison between two radiation schemes.

BACKGROUND: Our aim was to determine whether percutaneous endoscopic gastrostomy (PEG) dependence was significantly different between 2 prospective trials with different radiation fractionation schemes. METHODS: Stage III or IV locally advanced head and neck squamous cell carcinomas arising from the oral cavity, hypopharynx, oropharynx, nasopharynx, paranasal sinuses, or larynx were treated using hyperfractionation (A-3 protocol) or accelerated fractionation (A-4 protocol) with chemotherapy. Amifostine was administered 15 to 30 minutes preradiation, at a dose of 500 mg/day in both protocols. It was given as an infusion over 5 to 7 minutes (A-3 protocol) or subcutaneously (A-4 protocol). Data regarding PEG placement and removal were collected prospectively. RESULTS: Thirty-five evaluable A-3 protocol patients, 14 evaluable A-4 protocol patients, and 6 patients treated per A-4 protocol guidelines, but without amifostine as they refused the medication, were included in the analysis. Pretreatment characteristics, such as sex, age, race, T classification, N classification, American Joint Committee on Cancer (AJCC) stage, were compared between the 2 groups of patients. The only significant difference between the 2 groups was AJCC stage. Thirty-five A-3 patients and 20 A-4 patients had overall survivals of 88% versus 80%, 82% versus 75%, and 66% versus 67.5% at 1, 2, and 3 years, respectively (p = .958). With regard to PEG dependence, no significant differences were seen between the 2 groups at 6, 12, or 18 months. CONCLUSION: PEG dependence was not significantly different between the 2 study groups. Type of altered fractionation scheme may not influence PEG dependence in patients treated with similar protocols. Future randomized studies are needed to confirm these findings.

Small cell carcinoma of the head and neck: the university of Miami experience.

PURPOSE: To describe the University of Miami experience in the treatment of small cell carcinoma of the head and neck. METHODS AND MATERIALS: A total of 12 patients with nonmetastatic small cell carcinoma of the head and neck were treated between April 1987 and September 2007. Radiotherapy was the primary local treatment modality for 8 patients. RESULTS: Of the 12 patients, 8 had died after a median follow-up of 13 months. The 4 patients who were alive were followed for a median of 14 months. The Kaplan-Meier estimate of the proportion of small cell head-and-neck cancer patients surviving to 1 and 2 years was 63% and 26%, respectively. The percentage of patients remaining disease free at 1 and 2 years was 71% and 44%, respectively. The patients with tonsil/parotid gland cancer had significantly greater disease-specific survival compared with the other patients. The median survival time was 30 months in the tonsil/parotid group compared with 15.2 months in the other group (patients with small cell carcinoma of the sinonasal cavity, nasopharynx, and larynx). A total of 4 patients developed recurrence, 3 of whom had a distant failure component. The treatment modality was not associated with a difference in disease-specific survival. The 1-year disease-specific survival rate was 73% in the radiotherapy or radiotherapy/chemotherapy group compared with 67% in the other group. CONCLUSION: Radiotherapy with or without chemotherapy is a reasonable alternative to surgery for patients with small cell carcinoma of the head and neck. Patients with tonsillar or parotid small cell carcinomas did better than other sites. More aggressive treatment might be warranted for patients with sinonasal carcinoma. The outcome, however, continues to be suboptimal, and more effective therapy is needed because most patients had a component of local and distant failure.

WR-1065, the active form of amifostine, protects HL-60 cells but not peripheral blood mononuclear cells from radiation and etoposide-induced apoptosis.

PURPOSE: Developing myeloid cells are particularly sensitive to chemotherapy and ionizing radiation. Mature cells of the hematopoietic lineages, such as are found in the peripheral blood mononuclear cells (PBMCs), are much less sensitive for reasons that are not yet understood. Protecting the myeloid precursors from radiation or chemotherapy is an important goal. METHODS: We have used fluorescence microscopy to assess the ability of WR-1065, the active metabolite of amifostine (Ethyol), to protect cultured myeloid leukemic HL-60 cells or freshly isolated PBMCs from the induction of apoptosis by ionizing radiation or etoposide. RESULTS: WR-1065 greatly reduced the percentage of radiation-induced apoptosis in the p53 negative HL-60 cells 24 h after exposure to 8 Gy. WR-1065 also greatly reduced the percentage of HL-60 cells undergoing apoptosis 24 h after a 1-h exposure to 1 microM etoposide. The pan-caspase inhibitor ZVAD-fmk completely inhibited radiation-induced apoptosis in HL-60 cells when present for the first hour after exposure to radiation, but had no effect on cell survival. In contrast, neither WR-1065 nor ZVAD-fmk reduced the level of radiation-induced apoptosis in normal human PBMCs. CONCLUSION: These results suggest that pro-apoptotic pathways are present in immature myeloid cells that can be selectively protected from radiation or chemotherapy-induced apoptosis.