Joseph Valentino

Long-Term Result of Vocal Cord Augmentation with Autogenous Fat

The use of autogenous fat for augmentation of the paralyzed vocal fold is a promising substitute for alternate injectable material such as Teflon (polytef paste, polytetrafluoroethylene; Ethicon) and Gelfoam (absorbable gelatin sponge; Upjohn). Long-term histologic evaluation of fat grafts to the larynx has not previously been reported in the literature. We present a case report of autogenous fat augmentation of a paralyzed vocal fold with documentation of persistent fat graft present 5 months after transplant

Expected neurologic outcomes for surgical treatment of cervical neurilemomas

Objective: Neurilemomas are classically described as fusiform tumors that eccentrically displace the undisturbed neural fascicles. The authors seek to clarify the relationship of cervical neurilemomas to their nerve of origin and assess the functional outcome of surgical extirpation. Study Design: A retrospective review of clinical, intraoperative, and histopathologic data of six patients with cervical extracranial neurilemomas. Methods: Additional histochemical staining of the pathologic specimens was performed to evaluate the tumor for neurites. A comprehensive literature review of cervical neurilemoma cases and meta‐analysis of clinical outcomes in these cases were performed. Results: In the series of five consecutive cervical neurilemomas, only one was an eccentric mass pushing the undisturbed nerve aside. In the five other cases, excision of the neurilemoma required complete nerve excision. Neural elements traveling through the central portions of the tumor were clearly demonstrated histologically. Collective analysis of the literature on cervical neurilemomas revealed that although some cases allow nerve preservation, preservation of function is frequently poor. Conclusions: This experience and that reported in the literature suggest that it is frequently impossible to preserve the function of the nerve of origin with surgical treatment of cervical neurilemomas.

Accuracy of self-reported tobacco assessments in a head and neck cancer treatment population.

Prospective analysis was performed of self-reported and biochemically confirmed tobacco use in 50 head and neck cancer patients during treatment. With 93.5% compliance to complete weekly self-report and biochemical confirmatory tests, 29.4% of smokers required biochemical assessment for identification. Accuracy increased by 14.9% with weekly vs. baseline self-reported assessments. Data confirm that head and neck cancer patients misrepresent true tobacco use during treatment.

Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck

This study evaluated the combined effect of Low Dose Fractionated Radiation (LDFRT) and Taxotere (TXT) therapy on the growth of SCCHN (squamous cell carcinoma of head and neck; SQ-20B, a p53 mutant SCCHN cell line) tumors in a nude mouse model to exploit the increased hyper radiation sensitivity (HRS) phenomenon present in G2M cell cycle phase when induced by low doses of radiation that was demonstrated in in-vitro settings. Seventy-eight animals were randomized into one control group and 5 treatment groups (treatments were administered weekly for six weeks). Tumor regression was observed in all the groups, however, tumor regression was not significant in 2 Gy or TXT or 2 Gy plus TXT treated groups when compared to control group. The tumor regression was significant in both the LDFRT group (p

A Phase 2 Trial of Surgery With Perioperative INGN 201 (Ad5CMV-p53) Gene Therapy Followed by Chemoradiotherapy for Advanced, Resectable Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Hypopharynx, and Larynx Report of the Southwest Oncology Group

OBJECTIVE To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy. DESIGN AND SETTING A phase 2 study in a multi-institutional setting within the Southwest Oncology Group. PATIENTS Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease. INTERVENTIONS Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy. MAIN OUTCOME MEASURES Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201. RESULTS All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%. CONCLUSIONS This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00017173.

Delivery of RNA Nanoparticles into Colorectal Cancer Metastases Following Systemic Administration

The majority of deaths from all cancers, including colorectal cancer (CRC), is a result of tumor metastasis to distant organs. To date, an effective and safe system capable of exclusively targeting metastatic cancers that have spread to distant organs or lymph nodes does not exist. Here, we constructed multifunctional RNA nanoparticles, derived from the three-way junction (3WJ) of bacteriophage phi29 motor pRNA, to target metastatic cancer cells in a clinically relevant mouse model of CRC metastasis. The RNA nanoparticles demonstrated metastatic tumor homing without accumulation in normal organ tissues surrounding metastatic tumors. The RNA nanoparticles simultaneously targeted CRC cancer cells in major sites of metastasis, such as liver, lymph nodes, and lung. Our results demonstrate the therapeutic potential of these RNA nanoparticles as a delivery system for the treatment of CRC metastasis.

High-Dose Intra-Arterial Cisplatin Boost With Hyperfractionated Radiation Therapy for Advanced Squamous Cell Carcinoma of the Head and Neck

PURPOSE To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

Spatially Fractionated GRID Radiation Treatment of Advanced Neck Disease Associated with Head and Neck Cancer

Advanced nodal disease associated with head and neck cancer warrants aggressive, often multi-modality therapy to maximize local-regional control. The expansion of a novel treatment paradigm developed by our institution includes the addition of a single-fraction of high dose spatially-fractionated radiation (GRID) to a conventional course of treatment. Between 1995 and 2002 a series of 27 patients (median age 65) with bulky N2-3 disease were treated. Median nodal tumor size was 7 cm. Two groups of patients were evaluated. Group 1 (N=14) patients received a median neck dose 69 Gy (range 54–79 Gy) plus GRID treatment. Group 2 (N=13) patients received a median neck dose of 59 Gy (range 54–72 Gy) plus GRID treatment followed by planned neck dissection. Patients were evaluated for local-regional control, pathological response, survival, and morbidity. Median time to follow-up for Group 1 was 10 months (range 3–44 months). Neck control was 93%. Disease specific survival was 50%. Morbidity was limited to soft-tissue related damage and was mild. Median time to follow-up for Group 2 was 38 months (range 5–116 months). Pathologic complete response rate was 85%. Overall neck control rate was 92%. Disease specific survival was 85%. Surgical morbidity was limited to three wound healing complications. GRID treatment may be safely added to conventional treatment management of locally advanced neck disease related to cancer with acceptable morbidity. It may improve pathologic complete response rates in those patients who undergo planned neck dissection, possibly leading to improved survival. In patients with inoperable bulky disease, addition of GRID enhances local-regional control.

The Communicating Vein and Its Use in the Radial Forearm Free Flap

Thrombosis is the most frequent cause of failure in microvascular free‐tissue transfer. The large communicating vein of the cubital fossa connects the deep and superficial venous drainage of the radial forearm free flap (RFFF). This vein allows the surgeon to simultaneously drain both systems by means of the large veins of the cubital fossa. We prospectively collected data on the venous anatomy of the cubital fossa in 40 consecutive RFFFs over a 3‐year period. We then retrospectively reviewed available data from the 14 cases preceding the cases in the prospective series. At least 78% of our patients had a communicating vein that facilitated dual venous drainage; 87% of our RFFFs were drained by both the superficial and deep venous systems, and 90% of our RFFFs had two or more venous anastomoses. We had no RFFF failures in our series of 54 flaps. We present our venous anatomy findings in this series of forearms as well as the venous anastomoses of our 54 patients. The surgical‐flap harvest, including the communicating vein and its use, may provide an advantage in the dependability and quality of venous outflow.

Postoperative radiation therapy for primary vs. recurrent squamous cell carcinoma of the head and neck: Results of a comparative analysis

There is little literature comparatively evaluating the results of postoperative radiation therapy (RT) for patients with squamous cell carcinoma (SCC) of the head and neck treated for primary versus recurrent disease.