Biomedical subjects

David I Rosenthal

Publications and source records attributed to David I Rosenthal.

12 recordsLinked to original sources

PubMed2003

Sarcomatoid carcinoma of the head and neck: molecular evidence for evolution and progression from conventional squamous cell carcinomas.

The underlying events associated with the development of sarcomatoid head and neck squamous carcinoma and the biologic significance remain unknown. To investigate the genetic events involved in the evolution of this entity, comparative analysis of matched microdissected epithelial and sarcoma-like components from 11 primary sarcomatoid carcinomas was performed using microsatellite markers. Nine markers on chromosomes 4p, 9p, and 17p regions (3 per each chromosomal region) were selected based on their informativeness, small product size, and the high alterations in head and neck squamous carcinomas. In this study, loss of heterozygosity (LOH) in at least one marker in either component was noted in all 11 tumors, and instability was found in 10 instances (six in 3 paired specimens and four in the sarcomatoid area only). Concordant results in both components were found in 58 (79.5%) reactions (37 LOH and 21 retention of heterozygosity), and paradoxical findings were noted in 15 instances (20.5%). The latter included LOHs in only two conventional epithelial components and 13 sarcomatoid components. Both keratin-positive and -negative sarcomatoid tumors had a comparable frequency of LOH. The most frequently altered markers in both components were D9S168 and D9S171 (75% each) and D4S1587 (66%). The sarcomatoid components manifested distinctly high alterations at marker D17S520 on chromosome 17p. Our study supports: 1) an evolution of sarcomatoid carcinoma from the conventional epithelial-type, 2) a malignant nature of the sarcomatoid component, and 3) that molecular progression is associated with the sarcomatoid transformation.

Adult↗

PubMed2002

Organ preservation therapy using induction plus concurrent chemoradiation for advanced resectable oropharyngeal carcinoma: a University of Pennsylvania Phase II Trial.

PURPOSE: To determine the efficacy, feasibility, and toxicity of a new regimen for locally advanced oropharyngeal carcinoma. PATIENTS AND METHODS: Patients had technically resectable stage III/IV squamous cell carcinoma of the oropharynx, exclusive of T1-2N1. Induction chemotherapy consisted of carboplatin (area under the curve formula equal to 6) and paclitaxel 200 mg/m(2) for two cycles, followed by re-evaluation. Patients with major response continued to definitive radiotherapy (70 Gy over 7 weeks) plus concurrent once-weekly paclitaxel (30 mg/m(2)/wk). Patients with advanced neck disease also underwent post-radiation therapy neck dissection and two more chemotherapy cycles. RESULTS: Fifty-three patients were enrolled. Median follow-up was 31 months (minimum follow-up for survivors was 18 months). The major response rate to induction chemotherapy was 89%; 90% of patients had a complete response after concurrent chemoradiation. Actuarial survival at 3 years was 70%, and 3-year event-free survival was 59%. The 3-year actuarial locoregional control was 82% and the 3-year actuarial rate of distant metastases was 19%. Organ preservation was achieved in 77% of all patients. One patient (2%) died during therapy. Late grade 3 toxicity occurred in 24% of patients, consisting mainly of chronic dysphagia/aspiration and/or radiation soft tissue ulceration. The treatment-related mortality rate was 4% (two patients died from respiratory failure). CONCLUSION: Response to induction chemotherapy as studied in this trial was not useful as a predictive marker for ultimate outcome or organ conservation. Overall, however, this regimen offers good disease control and survival for patients with locally advanced oropharyngeal carcinoma, comparable with other concurrent chemoradiation programs. Further study of similar protocols is indicated.

Actuarial Analysis↗

PubMed2002

Parotidectomy in the treatment of aggressive cutaneous malignancies.

BACKGROUND: Aggressive nonmelanoma skin cancer (ANMSC) of the head and neck may require parotidectomy because of neurotropic spread, direct invasion of the parotid gland, or parotid metastasis. OBJECTIVE: To review our experience with parotidectomy in the treatment of these tumors to examine the indications for this procedure and to analyze treatment outcomes. We emphasize the importance of early identification of an ANMSC and a systematic approach to treatment. DESIGN: Review of 23 patients with an ANMSC who required parotidectomy with or without facial (VII) nerve sacrifice between January 5, 1996, and December 27, 1999. Median follow-up for all patients was 24 months. SETTING: Academic tertiary care referral center. PATIENTS: This study focused on 23 (median age, 71 years) of 54 patients treated for an ANMSC. Most tumors were in the periauricular (n = 9) and the frontozygomatic (n = 6) areas. Seven patients presented with facial weakness or paralysis. Three patients had clinically evident parotid metastasis, while 14 patients had tumors directly invading the parotid gland. Eighteen patients had recurrent disease that had been treated previously with Mohs micrographic surgery. INTERVENTIONS: Following wide local excision of the ANMSC, 12 patients had resection of the lateral parotid lobe with preservation of the nerve, while 11 required radical parotidectomy with sacrifice of 1 or more branches. Nineteen patients received cervical lymphadenectomy. Postoperative radiotherapy was administered in 19 patients. MAIN OUTCOME MEASURES: Tumor pathologic findings (specifically, perineural invasion of the facial nerve), locoregional control or recurrence, disease-free survival, disease-specific survival, and overall survival. RESULTS: Neurotropic spread to the facial nerve was present in 6 patients and was more likely to occur in younger patients (51 vs 75 years, P =.006). Locoregional failures occurred in 9 patients following treatment. Patients who required parotidectomy in their surgical treatment for an ANMSC were more likely to have recurrent disease (P =.0002). Disease-specific and overall survival was 79% and 69%, respectively, at 42 months. CONCLUSIONS: Patients with ANMSC may require parotidectomy in the context of neurotropic spread, regional metastasis, or direct invasion into the parotid gland. Surgery combined with postoperative radiotherapy is necessary in most patients because of adverse clinical and pathologic findings. A systematic approach to the management of the parotid and facial nerve in the presence of these aggressive tumors is required. Despite comprehensive treatment, local recurrence of ANMSC and mortality remain high.

Aged↗

PubMed2002

Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck.

BACKGROUND: To determine the effect of treatment time-related factors on outcome in patients treated with surgery and postoperative radiation therapy (RT) for locally advanced squamous cell carcinoma of head and neck (SCCHN) METHODS: A retrospective review was performed on 208 consecutive patients treated from 1992 to 1997 with surgery and postoperative RT (> or =55 Gy) for SCCHN. The treatment time factors considered were (1) interval from surgery to the start of RT; (2) RT duration; and (3) the total time from surgery to completion of RT (treatment package time). Treatment package time was dichotomized into short (< or =100 days) vs long (>100 days) categories. Other variables considered were clinical and pathologic staging, margin status, RT dose, and tumor site. Patients were also divided into intermediate- and high-risk groups on the basis of eligibility for RTOG 95-01. Univariate (logrank) and multivariate analyses were performed. RESULTS: Median follow-up for surviving patients was 24 months. Actuarial 2-year locoregional control (LRC) and survival rates were 82% and 71%, respectively. In univariate analysis, factors associated with higher locoregional failure were high-risk group (p =.011), margin status (p =.038), pathologic stage (p =.035), clinical N stage (p =.006), package time (p =.013), and RT treatment time (p =.03). Package time was also a significant predictor of survival in univariate analysis (p =.021). The other two individual time factors, tumor factors, and RT dose were not significant. Both risk status and treatment package time were significant factors in a multivariate model of LRC. CONCLUSIONS: A total treatment package time of <100 days is associated with improved tumor control and survival. Every effort should be made to keep the time from surgery to the completion of postoperative RT to <100 days.

Adult↗

PubMed2002

Desmoplastic neurotropic melanoma of the head and neck: the role of radiation therapy.

BACKGROUND: Desmoplastic neurotropic melanoma (DNM) is an uncommon cutaneous melanoma variant with pronounced neurotropism. In contrast to ordinary melanomas, locoregional recurrences are common and distant metastasis are uncommon in patients with DNM. Local control with surgery and radiation therapy may assume a more important role in this variant of melanoma. We present a case of an unresectable skull base recurrence of DNM that was controlled using radiation therapy alone and review the literature. METHODS: Case report with 36-month follow-up. RESULTS: The patient is a 68-year-old with multiple recurrences of a DNM that originated on the forehead. After extensive surgery, including total parotidectomy and temporal bone resection, the patient had an unresectable recurrence of the skull base develop. This was treated with definitive radiation therapy, resulting in a complete response. The patient has had no evidence of recurrence at 3 years. CONCLUSIONS: DNM is a locally aggressive type of melanoma with a high risk of local recurrence that can be radioresponsive. The incidence of distant metastasis is low, so aggressive treatment to control local disease is warranted. This may include surgery plus adjuvant radiation therapy or definitive radiotherapy for unresectable recurrences.

Aged↗

PubMed2002

Prediction of treatment response of head and neck cancers with P-31 MR spectroscopy from pretreatment relative phosphomonoester levels.

RATIONALE AND OBJECTIVES: Combinations of chemotherapy and fractionated radiation therapy are the currently preferred nonsurgical treatment methods for squamous cell carcinoma of the head and neck, but to the authors' knowledge there is no reliable marker for predicting therapeutic response. Early identification of nonresponders would allow prompt replacement of ineffective, toxic therapy by alternative, potentially more effective procedures. Frequent regional node involvement facilitates surface coil investigation with phosphorus-31 magnetic resonance spectroscopy. MATERIALS AND METHODS: P-31 magnetic resonance spectra were acquired from 12 patients before radiation therapy or chemotherapy. In vivo three-dimensional localized P-31 nuclear magnetic resonance chemical shift imaging was performed with a 1.5-T clinical imager and a dual-tuned H-1/P-31 surface coil. Proton decoupling and nuclear Overhauser enhancement were used to improve sensitivity and resolve overlapping signals in the phosphomonoester region of the spectrum. RESULTS: The average pretreatment ratio of phosphomonoester to beta-nucleoside triphosphate was significantly smaller in complete responders (n = 4) than in incomplete responders (partial responders plus nonresponders, n = 8) (0.0 +/- 0.0 vs 1.22 +/- 0.17 [P = .004]). CONCLUSION: Results of this preliminary study suggest that H-1-decoupled P-31 magnetic resonance spectroscopy may prove to be a useful predictor of therapeutic response in head and neck cancers.

Adult↗

PubMed2002

A phase I study of SPI-077 (Stealth liposomal cisplatin) concurrent with radiation therapy for locally advanced head and neck cancer.

BACKGROUND: Liposomal cisplatin preparations have two potential advantages over the free drug when combined with radiation therapy (RT): 1) selective tumor localization, improving the therapeutic ratio, and 2) prolonged half-life, allowing more radiosensitization. We performed a Phase I study of Stealth liposomal cisplatin (SPI-077) concurrent with RT for head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with Stage IVa/b HNSCC were treated with SPI-077, given intravenously twice two weeks apart, concurrent with RT (60-72 Gy in 6-7 weeks). The SPI-077 dose was escalated in standard phase I design. RESULTS: Twenty patients received 38 doses of SPI-077, escalated from 20-200 mg/m2 in six dose levels. Two of these patients received one dose because of reversible Grade 3 liver toxicity or rash. Three patients had a Grade 1, and one had a Grade 2 infusion reaction. Four patients had transiently elevated transaminases: Grade I (n = 1), Grade 2 (n = 1), and Grade 3 (n = 2). Grade 3 neutropenia occurred in one patient. There was no ototoxicity, neurotoxicity, or nephrotoxicity. In-field radiation skin and mucosal toxicities did not appear to be intensified. Ten of 17 patients (59%) finishing treatment achieved initial complete response. CONCLUSIONS: Systemic and in-field radiation toxicities of SPI-077 were minimal. Infusion reactions were minimized with a slower and more dilute initial infusion. Further dose escalation was stopped in the absence of dose-limiting toxicity to address the reformulation of the liposomally bound cisplatin. Nonetheless, this study shows that high doses of SPI-077 can be given safely. The potentially beneficial therapeutic ratio suggests that liposomal radiosensitizer preparations warrant further investigation.

Adult↗

PubMed2002

Nasopharyngeal carcinoma treated with external radiotherapy, brachytherapy, and concurrent/adjuvant chemotherapy.

The standard treatment for advanced nasopharyngeal carcinoma (NPC) has become external beam radiation therapy (EBXRT) 70 Gy/7 weeks + 3 cycles of concurrent cisplatin followed by 2 to 3 cycles of adjuvant cisplatin/5-fluorouracil (5-FU). Some reports suggest that the addition of low-dose rate brachytherapy to EBXRT also improves local control. To our knowledge, this is the first report of the "triple" combination of EBXRT, brachytherapy, and concurrent/adjuvant chemotherapy. Eleven patients treated from 1992 to 1998 were evaluated. All patients had stage III/IV (excluding T4 lesions) NPC. Treatment consisted of EBXRT (64-70 Gy/7 weeks), followed by a brachytherapy boost (6-15 Gy delivered 0.5 cm deep to the mucosa). Chemotherapy consisted of concurrent cisplatin (100 mg/m2) and post-XRT adjuvant cisplatin (80 mg/m2) and 5-FU (1,000 mg/m2/day x 4 days) for 2 cycles. All 11 patients were evaluable. The average age was 44 years, and median follow-up was 38 months (range: 23-82 months). Median EBXRT dose was 66 Gy, and median brachytherapy dose was 9 Gy (median total dose: 75 Gy). All patients obtained primary tumor complete response (CR). Two patients required post-XRT neck dissection to achieve regional CR. To date, 10 patients are alive with no evidence of disease. The 3-year actuarial survival is 100%. One patient died at 82 months of a late distant recurrence (at 37 months post-XRT). No patient has had a local or neck failure. Chemoradiation plus brachytherapy offers encouraging survival and local-regional control. Further study of this regimen as an alternative or adjunct to intensity-modulated EBXRT is warranted.

Adolescent↗

PubMed2002

Relative risk of stroke in head and neck carcinoma patients treated with external cervical irradiation.

OBJECTIVE: To determine the rate of cerebrovascular events (stroke) in patients irradiated to high doses for squamous cell carcinoma of the head and neck. STUDY DESIGN: Retrospective chart review of 413 patients treated from 1987 to 2000 with squamous cell carcinoma of the head and neck was performed to determine the risk of stroke compared with the expected rate. METHODS: Surgical, radiotherapeutic, radiological, and clinical or office records of 413 patients were analyzed, and data were collected regarding clinical risk factors for stroke, irradiation parameters, and follow-up on whether or not a stroke event occurred. The actuarial risk of stroke for this population was calculated and compared with expected risk from population-based data. RESULTS: Of the 413 patients, 20 had strokes in follow-up, occurring between 2 and 146 months after radiotherapy. The 5-year actuarial rate of stroke was 12%, which corresponded to a relative risk of 2.09 ( P=.0007) compared with the population-based "expected" data. Median radiation therapy dose was 64 Gy; there was no correlation between radiation therapy dose and stroke risk. No correlation was identified between surgery near the carotids and stroke risk. CONCLUSIONS: An association between high-dose cervical irradiation for squamous cell carcinoma of the head and neck and stroke is demonstrated. Although the relative risk is approximately doubled, the absolute risk is modest in comparison to the risk of cancer recurrence. Further study of this association and possible interventions is warranted.

Aged↗

PubMed2002

Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction.

PURPOSE: Locoregional recurrence is the dominant form of treatment failure in head and neck (H&N) cancer. The epidermal growth factor receptor (EGFR) is frequently amplified in this disease (<or=80%) and can lead to activation of phosphatidylinositol-3-kinase (PI3K), both directly and indirectly through Ras. We have shown previously that radioresistance could be conferred via the Ras-PI3K pathway. Here we investigate the contribution of EGFR to this pathway and its impact on treatment outcome. EXPERIMENTAL DESIGN: In a series of 38 H&N cancer patients, overexpression of EGFR by immunohistochemical staining was assessed. PI3K signaling was evaluated by staining for phosphorylated Akt (P-Akt), a downstream target of PI3K. Both EGFR and P-Akt were then related to outcome. Radiation survival was determined in the SQ20B cell line, a radioresistant squamous cell line derived from a recurrent laryngeal cancer, after pharmacological blockade of EGFR with Iressa, of Ras by the FTI L744,832, or of PI3K by LY294002. RESULTS: A significant association was found between P-Akt staining and local control in the patient series. Two-year local control was 100% for patients staining 0-1+ for P-Akt as compared with 70.6% for patients staining 2-3+ (P = 0.04). In our series of 38 H&N cancers, 30 (78.9%) of the specimens were strongly (3+) positive for EGFR, whereas 25 (65.8%) were moderately to strongly (2-3+) positive for P-Akt. Pharmacologically inhibiting EGFR, Ras, and PI3K led to radiosensitization of SQ20B cells. CONCLUSIONS: Evaluation of PI3K activation by Akt phosphorylation might be a prognostic marker for response to therapy, and PI3K could be a useful target for therapy. These results also suggest that signaling from EGFR to PI3K can lead to radioresistance.

Adult↗

PubMed2002

Validating a dipstick method for detecting recent smoking.

This report evaluates the validity of a new method for verifying self-reported smoking status in patients presenting for pulmonary medicine treatment. A prospective comparison was made between self-reports of smoking status and a new semiquantitative, enzyme-linked, immunosorbent assay-based method testing for the presence of a prime nicotine metabolite, cotinine. Results were validated by gas chromatography/mass spectrometry. Data were collected in an urban, academic, tertiary health care setting. The study included 76 consecutive new patients presenting to participating clinical practices at the Pulmonology or Thoracic Surgery Services. Before taking a smoking history, patients were informed that their urine would be tested onsite for the presence of nicotine using a new method, the NicoMeter, for determining tobacco product exposure, followed by more standard laboratory testing. The level of agreement between the biochemical measurement types was excellent, kappa = 0.777. The new biochemical measurement type used was easy to use. Self-reported smoking status corresponded closely to biochemical testing. However, there was a 5.3-9.5% misclassification of smoking status among the group studied, depending upon the measurement type used. Among 32 lung cancer patients, 15.6%, most likely misrepresented their current smoking status. The NicoMeter appears to be a valid and useful method for confirming self-reported smoking status. Lung cancer patients had a higher rate of inaccurate nonsmoking compared with patients with nonmalignant pulmonary disease. The findings have implications for investigators who accept self-reported smoking status without biochemical verification.

Aged↗

PubMedDate not supplied

Reinterpretation of cross-sectional images in patients with head and neck cancer in the setting of a multidisciplinary cancer center.

BACKGROUND AND PURPOSE: Patients referred to tertiary care centers frequently arrive with images obtained at outside institutions; these images require reinterpretation. We assessed the clinical value of reinterpreting cross-sectional imaging studies of patients with head and neck cancer, in the setting of a multidisciplinary cancer center. METHODS: Outside CT and MR images of 136 patients with known or presumed head and neck cancer were reinterpreted by a neuroradiologist. Clinical history and findings on physical examination were available. Reinterpretation was performed before review of outside reports, which were subsequently compared with those generated at the cancer center. Changes in interpretation were noted, and their effects on TNM staging, patient care, and prognosis were assessed. Reliability and statistical significance of rates of change in diagnosis were analyzed with 95% confidence intervals (CIs) and the sign test, respectively. Verification of change in diagnosis was confirmed by pathologic analysis (75%), characteristic radiologic findings (18%), or clinical and imaging follow-up (7%). RESULTS: Change in interpretation occurred in 56 patients (41%) (95% CI: 33-49%, P <.001). Forty-six patients (34%) had a change in T, N, and/or M staging (26-42%, P <.001). Change in T stage occurred in 27 cases (20%) (13-27%, P <.001) (upstaged in 22, downstaged in five), and a change in N stage in 26 cases (19%) (12-26%, P <.001) (upstaged in 20, downstaged in six). Two patients (1.5%) had missed systemic metastases. Three patients with an initial diagnosis of cancer were found to be cancer-free, and six patients had a diagnosis of new second primary cancers that were missed at original interpretation. One patient had a missed middle cerebral artery aneurysm. Changes in image interpretation altered treatment in 55 (98%) of 56 patients and affected prognosis in 53 patients (95%) (P <.001). CONCLUSION: Reinterpretation of cross-sectional images in the setting of a multidisciplinary cancer center has a significant effect on staging, management, and prognosis in patients with head and neck cancer.

Academic Medical Centers↗