Publications by authors named "Harlan A Pinto"

25 Publications

  • Page 1 of 1

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 07;18(7):873-898

29National Comprehensive Cancer Network.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
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http://dx.doi.org/10.6004/jnccn.2020.0031DOI Listing
July 2020

Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer.

J Clin Oncol 2019 12 16;37(34):3266-3274. Epub 2019 Oct 16.

Yale University School of Medicine, New Haven, CT.

Purpose: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved.

Results: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; = .22). At 2, 3, and 4 years, the OS rates were 25.2% 18.1%, 16.4% 10.0%, and 11.8% 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; = .10), with a median OS of 14.2 months on BC 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months 4.3 months with chemotherapy ( = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy ( = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% 0.5%; < .001) and treatment-related deaths (9.3% 3.5%; = .022) with BC versus chemotherapy.

Conclusion: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.
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http://dx.doi.org/10.1200/JCO.19.00555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980834PMC
December 2019

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

J Natl Compr Canc Netw 2018 05;16(5):479-490

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.
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http://dx.doi.org/10.6004/jnccn.2018.0026DOI Listing
May 2018

Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590).

Cancer 2017 Dec 7;123(23):4653-4662. Epub 2017 Aug 7.

Department of Medicine Hematology/Oncology, University of Rochester Medical Center, Rochester, New York.

Background: 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS).

Methods: In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups.

Results: 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis.

Conclusions: Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693641PMC
December 2017

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017.

J Natl Compr Canc Netw 2017 06;15(6):761-770

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.
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http://dx.doi.org/10.6004/jnccn.2017.0101DOI Listing
June 2017

Head and Neck Cancers, Version 1.2015.

J Natl Compr Canc Netw 2015 Jul;13(7):847-55; quiz 856

From Memorial Sloan Kettering Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; Duke Cancer Institute; Yale Cancer Center/Smilow Cancer Hospital; Massachusetts General Hospital Cancer Center; Moffitt Cancer Center; Vanderbilt-Ingram Cancer Center; Stanford Cancer Institute; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Mayo Clinic Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; Dana-Farber/Brigham and Women's Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; Roswell Park Cancer Institute; Huntsman Cancer Institute at the University of Utah; University of Colorado Cancer Center; The University of Texas MD Anderson Cancer Center; Fred & Pamela Buffett Cancer Center; City of Hope Comprehensive Cancer Center; UC San Diego Moores Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; University of Michigan Comprehensive Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; and National Comprehensive Cancer Network.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976490PMC
http://dx.doi.org/10.6004/jnccn.2015.0102DOI Listing
July 2015

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

J Natl Compr Canc Netw 2014 Oct;12(10):1454-87

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."
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http://dx.doi.org/10.6004/jnccn.2014.0142DOI Listing
October 2014

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

J Natl Compr Canc Netw 2013 Aug;11(8):917-23

From 1Memorial Sloan-Kettering Cancer Center; 2The University of Texas MD Anderson Cancer Center; 3Duke Cancer Institute; 4Fox Chase Cancer Center; 5Massachusetts General Hospital Cancer Center; 6Moffitt Cancer Center; 7Vanderbilt-Ingram Cancer Center; 8Stanford Cancer Institute; 9The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 10The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 11Dana-Farber/Brigham and Women's Cancer Center; 12Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; 13Roswell Park Cancer Institute; 14Huntsman Cancer Institute at the University of Utah; 15UNMC Eppley Cancer Center at The Nebraska Medical Center; 16City of Hope Comprehensive Cancer Center; 17University of Washington/Seattle Cancer Care Alliance; 18Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 19St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 20University of Alabama at Birmingham Comprehensive Cancer Center; 21University of Michigan Comprehensive Cancer Center; 22UCSF Helen Diller Family Comprehensive Cancer Center; and 23National Comprehensive Cancer Network.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).
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http://dx.doi.org/10.6004/jnccn.2013.0113DOI Listing
August 2013

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence.

Cancer 2013 Apr 7;119(7):1349-56. Epub 2012 Dec 7.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.

Background: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.

Methods: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans.

Results: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.

Conclusions: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.
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http://dx.doi.org/10.1002/cncr.27892DOI Listing
April 2013

A planned neck dissection is not necessary in all patients with N2-3 head-and-neck cancer after sequential chemoradiotherapy.

Int J Radiat Oncol Biol Phys 2012 Jul 2;83(3):994-9. Epub 2011 Dec 2.

Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-5847, USA.

Purpose: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease.

Methods And Materials: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed.

Results: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04).

Conclusion: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.
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http://dx.doi.org/10.1016/j.ijrobp.2011.07.042DOI Listing
July 2012

Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2008 Jun 31;71(2):393-400. Epub 2007 Dec 31.

Department of Radiation Oncology, Stanford University, Stanford, CA 94305-5847, USA.

Purpose: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).

Methods And Materials: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.

Results: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.

Conclusion: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.
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http://dx.doi.org/10.1016/j.ijrobp.2007.10.027DOI Listing
June 2008

Plasma osteopontin is an independent prognostic marker for head and neck cancers.

J Clin Oncol 2006 Nov;24(33):5291-7

Department of Radiation Oncology, Stanford University, Stanford, CA, USA.

Purpose: To confirm the relationship between plasma osteopontin (OPN) levels and treatment outcomes in head and neck squamous cell carcinoma (HNSCC) patients in an expanded study.

Patients And Methods: One hundred forty patients with newly diagnosed HNSCC were enrolled onto this study, 54 previously reported and 86 new patients. Pretreatment plasma OPN levels were assessed in all patients by an enzyme-linked immunosorbent assay method. OPN levels were correlated to treatment outcomes in the new group of patients. Detailed analyses were also performed on the relationship between OPN and tumor control rate, event-free survival (EFS), and postrelapse survival for the entire group.

Results: Using a previously defined cut off point of 450 ng/mL, there was a significant correlation between OPN and freedom-from-relapse (P = .047), overall survival (P = .019), and EFS (P = .023) in the new, independent patient cohort (n = 86). Sequence of event analyses using the entire group (N = 140) revealed that OPN was an independent prognostic factor for initial tumor control, EFS in those who have achieved tumor control, and postrelapse survival.

Conclusion: In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.
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http://dx.doi.org/10.1200/JCO.2006.06.8627DOI Listing
November 2006

Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas.

Cancer 2006 May;106(9):1940-9

Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA.

Background: The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC).

Methods: Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response.

Results: The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms.

Conclusions: The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.
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http://dx.doi.org/10.1002/cncr.21785DOI Listing
May 2006

Advanced-staged tonsillar squamous carcinoma: organ preservation versus surgical management of the primary site.

Head Neck 2006 Jul;28(7):587-94

Department of Radiation Oncology, 875 Blake Wilbur Dr, R. CC-G228, Stanford University, Stanford, CA 94305, USA.

Background: Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site.

Methods: The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy.

Results: No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group.

Conclusion: Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.
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http://dx.doi.org/10.1002/hed.20372DOI Listing
July 2006

Phase II trial of taxol in salivary gland malignancies (E1394): a trial of the Eastern Cooperative Oncology Group.

Head Neck 2006 Mar;28(3):197-204

Louisiana State University Medical Center, New Orleans, Louisiana, USA.

Background: Malignant tumors of the salivary glands make up approximately 5% of head and neck cancers. The Eastern Cooperative Oncology Group (ECOG) initiated a phase II evaluation of paclitaxel in patients with locally recurrent or metastatic salivary gland malignancies.

Methods: Chemo-naive patients with histologically confirmed recurrent or metastatic carcinoma of salivary gland origin (mucoepidermoid, adenocarcinoma, or adenoid cystic) were eligible. Patients were treated with paclitaxel, 200 mg/m(2) IV, every 21 days for a minimum of four cycles.

Results: Forty-five patients were treated. Eight partial responses were seen among the 31 patients with mucoepidermoid or adenocarcinoma histologic findings for a response rate of 26%. No responses were seen in the adenoid cystic carcinoma group. No significant difference in overall survival was found among these three histologic subgroups.

Conclusion: Paclitaxel demonstrates moderate activity in salivary gland tumors of mucoepidermoid and adenocarcinoma histology. The poor response rate in adenoid cystic carcinoma is consistent with prior reports in this chemoresistant histologic subtype.
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http://dx.doi.org/10.1002/hed.20327DOI Listing
March 2006

Positron-emission tomography for surveillance of head and neck cancer.

Laryngoscope 2005 Apr;115(4):645-50

Department of Otolaryngology--Head and Neck Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.

Objectives/hypothesis: To determine the diagnostic accuracy and the ideal timing of fluoro-fluorodeoxyglucose positron-emission tomography (PET) in the posttreatment surveillance of head and neck mucosal squamous cell carcinoma (HNSCC).

Study Design: Retrospective chart review.

Methods: Our sample includes 103 adult patients with 118 posttreatment PET scans who had undergone treatment for HNSCC. We correlated PET results with surgical pathology and clinical outcome in the subsequent 6 months.

Results: For the detection of locoregional persistent or recurrent HNSCC, PET scans had a sensitivity of 82%, specificity of 92%, positive predictive value (PPV) of 64%, negative predictive value (NPV) of 97%, and overall accuracy of 90%. For the detection of distant metastases, PET scans had a sensitivity of 89%, specificity of 97%, PPV of 85%, NPV of 98%, and overall accuracy of 96%. PET scans of the head and neck region performed greater than 1 month after the completion of radiation compared with scans performed within 1 month had a significantly higher sensitivity of 95% versus 55% (P < .01) and NPV of 99% versus 90% (P < .01).

Conclusion: PET is effective in detecting distant metastases in the posttreatment surveillance for HNSCC patients. A negative PET is highly reliable for all sites. However, a positive PET in the head and neck region is unreliable because of a high false-positivity rate. PET of the head and neck region has a statistically significant risk of a false-negative reading when performed within 1 month of radiation.
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http://dx.doi.org/10.1097/01.mlg.0000161345.23128.d4DOI Listing
April 2005

Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2003 Jul;56(4):1046-54

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305-5302, USA.

Purpose: Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.

Methods And Materials: Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.

Results: At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.

Conclusion: STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.
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http://dx.doi.org/10.1016/s0360-3016(03)00117-2DOI Listing
July 2003

Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in head-and-neck cancer patients.

Int J Radiat Oncol Biol Phys 2003 Jun;56(2):375-83

Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.

Purpose: To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas.

Materials And Methods: As part of a larger clinical trial, 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays, performed on fine-needle aspirates at 1 and 2 min after 5 Gy. Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min. Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis, and the distribution of values was quantified using median tail moment (MTM). Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response.

Results: There was a significant correlation between the 1- and 2-min MTM (slope = 0.77 +/- 0.03). There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo. No correlation was found between Eppendorf PO2 measurements and comet MTM. There was a statistically significant correlation between the treatment response in the node studied and comet MTMs, whereas no correlation was observed between treatment response and Eppendorf measurements.

Conclusions: Comet assays are reproducible, as shown by biopsies at 1 and 2 min. Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia. There was no correlation between Eppendorf PO2 measurements and comet MTM. Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome. Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals.
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http://dx.doi.org/10.1016/s0360-3016(02)04503-0DOI Listing
June 2003

Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas.

Clin Cancer Res 2003 Jan;9(1):59-67

Department of Radiation Oncology, Center for Clinical Science Research-South, Stanford, California 94305-5152, USA.

Purpose: Tumor hypoxia modifies treatment efficacy and promotes tumor progression. Here, we investigated the relationship between osteopontin (OPN), tumor pO(2), and prognosis in patients with head and neck squamous cell carcinomas (HNSCC).

Experimental Design: We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. Plasma OPN levels in 15 volunteers, 31 VHL patients, and 54 HNSCC patients were quantitatively measured by ELISA. The relationships between plasma OPN levels, tumor pO(2) as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated.

Results: Microarray analysis indicated that OPN gene expression inversely correlated with that of VHL. These findings were confirmed by Northern blot analysis. ELISA studies and Western blot in a HNSCC cell line demonstrated that hypoxia exposure resulted in increased OPN secretion. Patients with VHL syndrome had significantly higher plasma OPN levels than healthy volunteers. Plasma OPN level inversely correlated with tumor pO(2) (P = 0.003, r = -0.42). OPN levels correlated with clinical outcomes. The 1-year FFR and survival rates were 80 and 100%, respectively, for patients with OPN levels 450 ng/ml (P = 0.002 and 0.0005). Multivariate analysis revealed that OPN was an independent predictor for FFR and survival.

Conclusions: Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence.
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January 2003

Estimating DNA repair by sequential evaluation of head and neck tumor radiation sensitivity using the comet assay.

Arch Otolaryngol Head Neck Surg 2002 Jun;128(6):698-702

Division of Otolaryngology-Head and Neck Surgery, Stanford University Medical Center, R135, Edwards Bldg, Stanford, CA 94305-5328, USA.

Background: The alkaline comet assay is a microelectrophoretic technique for detecting single-strand DNA breaks, and may be used as an indirect measure of hypoxia by determining the radiation sensitivity of individual cells.

Objective: To assess the ability of the comet assay to estimate the rate of DNA repair after irradiation in patients with head and neck cancer.

Methods: The comet assay was used to evaluate DNA damage in fine-needle aspirates of lymph nodes containing metastatic squamous cell carcinoma in patients with head and neck cancer 1, 2, and 3 minutes after treatment with 500 rad (5 Gy) of irradiation. The amount of DNA damage (measured as the "tail moment" of the comet) is proportional to the number of DNA single-strand breaks after irradiation, which in turn depends on the oxygen concentration in each cell.

Results: The mean +/- SD of the median tail moment of the 1-minute postirradiation comets was 29.4 +/- 14.2 (n = 27). After 2 minutes, the mean median tail moment decreased to 25.4 +/- 13.6 (n = 25), representing a mean decrease of 11.9% in those patients with both 1- and 2-minute comet assays. Assuming a linear rate of repair, this decrease in DNA damage corresponds to a repair half-life of 4.2 minutes. A 3-minute assay was also performed on samples from a smaller number of patients (n = 9), with a mean value not significantly different from that of the 2-minute assay of the samples from this group.

Conclusions: The comet assay is a promising tool for evaluating radiation sensitivity in individual cells. The rate of DNA repair early after irradiation is consistent with data in the literature.
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http://dx.doi.org/10.1001/archotol.128.6.698DOI Listing
June 2002