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Five-year outcomes of squamous cell carcinoma of the tonsil treated with radiotherapy

Mourad, Waleed F; Hu, Kenneth S; Puckett, Lindsay; Hauerstock, David; Shourbaji, Rania A; Li, Zujun; Manolidis, Spiros; Schantz, Stimson; Tran, Theresa; Jacobson, Adam; Urken, Mark; Culliney, Bruce; Persky, Mark; Harrison, Louis B
PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.
PMID: 23357967
ISSN: 0277-3732
CID: 1261692

Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck

Mourad, Waleed F; Hu, Kenneth S; Shasha, Daniel; Concert, Catherine; Ishihara, Dan; Lin, Wilson; Shourbaji, Rania A; Ryniak, Magdalena; Gamez, Mauricio E; Lukens, John N; Li, Zujun; Culliney, Bruce E; Khorsandi, Azita S; Tran, Theresa; Jacobson, Adam; Manolidis, Spiros; Schantz, Stimson; Urken, Mark; Persky, Mark S; Harrison, Louis B
AIM: Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context. PATIENTS AND METHODS: Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%. RESULTS: At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%). CONCLUSION: RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.
PMID: 24403470
ISSN: 0250-7005
CID: 963302

Hypofractionated Palliative Radiation Therapy With Concurrent Chemotherapy for Advanced Head-and-Neck Cancer: The QUAD-Shot Regimen [Meeting Abstract]

Gamez, ME; Hu, K; Agarwal, M; Dhanireddy, B; Katz, Elena; Li, Z; Culliney, B; Harrison, LB
ORIGINAL:0011015
ISSN: 1879-355x
CID: 2048892

Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy

Limaye, Sewanti Atul; Haddad, Robert I; Cilli, Fiona; Sonis, Stephen T; Colevas, A Dimitrios; Brennan, Michael T; Hu, Kenneth S; Murphy, Barbara A
BACKGROUND: Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS: A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 x 10(11) , 6 x 10(11) , and 1.2 x 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS: AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced >/= 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS: AG013 was safe and well tolerated. Preliminary efficacy data support further study.
PMID: 24114811
ISSN: 0008-543x
CID: 1499022

Long-term outcome of seropositive HIV patients with head and neck squamous cell carcinoma treated with radiation therapy and chemotherapy

Mourad, Waleed F; Hu, Kenneth S; Shasha, Daniel; Concert, Catherine; Ishihara, Dan; Lin, Wilson; Gamez, Mauricio E; Lukens, John J; Shourbaji, Rania A; Ryniak, Magdalena; Li, Zujun; Culliney, Bruce E; Khorsandi, Azita S; Tran, Theresa; Jacobson, Adam; Manolidis, Spiros; Schantz, Stimson; Urken, Mark; Persky, Mark S; Harrison, Louis B
AIM: To report the outcome of radiation therapy (RT) +/- chemotherapy in HIV-seropositive patients with Head and Neck Squamous Cell Carcinoma (HNSCC). PATIENTS AND METHODS: This is the largest single-Institution retrospective study to date, consisting of 73 HIV patients with HNSCC treated from January 1997-2010. The median age at RT, HIV diagnosis and the duration of patients being HIV seropositive were 51, 34, and 11 years, respectively. Seventy patients had SCC and one had submandibular salivary duct carcinoma. Stages I-II, III and IVA/B were: 22%, 27% and 51%, respectively. Primary cancer sites comprised the larynx (37%), oropharynx (32%), oral cavity (13%), hypopharynx (7%), nasopharynx (4%), unknown primary (MUP) (4%), nasal cavity (3%), and submandibular salivary duct (1%). All patients had an ECOG performance scale of /=2. Xerostomia grade
PMID: 24324090
ISSN: 0250-7005
CID: 963292

Trimodality management of sinonasal undifferentiated carcinoma and review of the literature

Mourad, Waleed F; Hauerstock, David; Shourbaji, Rania A; Hu, Kenneth S; Culliney, Bruce; Li, Zujun; Jacobson, Adam; Tran, Theresa; Manolidis, Spiros; Schantz, Stimson; Urken, Mark; Persky, Mark; Harrison, Louis B
OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy with optimal management remains unclear. We performed a review of the impact of trimodality approach on SNUC outcome. METHODS: This is a single-institution retrospective study of 18 patients, who were managed between 1997 and 2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%) were female. Three patients had stage II disease and underwent surgery alone, 12 had stages III and IVa and underwent surgery combined with chemoradiation, and 3 had stage IVb and underwent definitive chemoradiation. Patients who underwent preoperative, postoperative, and definitive chemoradiation received 60, 66, and 70 Gy of radiation, respectively. In all patients receiving concurrent chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3 cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5-fluorouracil (TPF) every 3 weeks for 2 to 3 cycles. RESULTS: After a median follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%; 75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach provided 83% LC and 92% DM-free survival, whereas other modalities provided 50% LC and 33% DM-free survival. The causes of death for the entire cohort were DM and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2 dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and 6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11% retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3 peripheral neuropathy. CONCLUSIONS: SNUC is an aggressive neoplasm that frequently presents at an advanced stage. Our data show that trimodality approach in the form of surgery combined with chemoradiation seems to offer better LC and lower DM compared with other modalities.
PMID: 22992621
ISSN: 0277-3732
CID: 1261702

Long-term follow-up and pattern of failure for T1-T2 glottic cancer after definitive radiation therapy

Mourad, Waleed Fouad; Hu, Kenneth S; Shourbaji, Rania A; Woode, Rudolph; Harrison, Louis B
PURPOSE: To evaluate the impact of radiation therapy (RT) on the long-term outcomes and pattern of failure for T1-2 glottic cancer. MATERIALS AND METHODS: This is a single-institution, retrospective study. From January (1997 to 2010), 253 patients with early glottic cancer underwent RT by 2-dimensional or 3-dimensional RT with Co or linear accelerator. Appropriate daily bolus was applied with linear accelerator-based RT to avoid under dosage of the anterior commissure. RESULTS: A total of 253 patients with T1-T2 glottic cancer were treated with definitive RT. The median age was 65 and males made up 87% of the population. T1 was 77% of the population. The median dose and fraction size were 63 and 2.25 Gy, respectively. After a median follow-up of 83 months, the locoregional control (LRC) for the whole cohort was 98%. Specifically, LRCs for T1 (195 patients) and T2 (58 patients) were 99.5% and 91%, respectively. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. CONCLUSIONS: Single-modality RT provides an excellent and effective treatment for T1-T2 glottic cancer with remarkable functional preservation and 5-year LRC of 98% with negligible long-term toxicity.
PMID: 22868239
ISSN: 0277-3732
CID: 1499032

Comprehensive head and neck radiotherapy dose-volume constraints do not apply to smaller volumes

Mourad, Waleed F; Shasha, Daniel; Blakaj, Dukagjin M; Khorsandi, Azita S; Shourbaji, Rania A; Glanzman, Jonathan; Kabarriti, Rafi; Young, Rebekah; Patel, Shyamal; Katsoulakis, Evangelia; Gamez, Mauricio; Woode, Rudolph; Lazarus, Cathy; Concert, Catherine; Hu, Kenneth S; Harrison, Louis B
AIM: To investigate the impact of definitive radiation therapy (RT) in the management of early glottic cancer on clinical RT-induced dysphagia (RID) and carotid vasculopathy (RICV). PATIENTS AND METHODS: This is a single-institution retrospective study. From January 1997 to 2010, 253 patients, with early glottic cancer, underwent RT with (60)Co or LINAC-6 MV photons. RT fields with wedge pair and daily 5-mm bolus were applied in all patients treated with 6-MV photons to avoid under-dose of the anterior laryngeal structures. The whole larynx (LX), pharyngeal constrictors (PCs), and carotid arteries (CA) were contoured and dose-volume histograms (DVHs) were generated to assess the delivered dose. The median age of patients was 65 years (range; 28-93), Caucasians were 80%, males were 87%, and 23% had T2 lesions. RESULTS: After a median follow-up of seven years (range; 1.5-12), the median dose and fraction size delivered to the LX were 63 and 2.25 Gy, respectively. The mean doses to the LX, PC, and CA were 57 Gy delivered to 34 cm(3), 54 Gy to 15 cm(3), and 60 Gy to 4 cm(3), respectively. The LX, PC and CA V60 and V65 were (77 and 71), (70 and 52) and (84 and 51), respectively. Patients with acute dysphagia grades 1, 2, and 3 or more were 81, 19%, and zero, respectively; none had clinically RID or RICV. CONCLUSION: Small-volume RT up to 67.5 Gy at 2.25 Gy per fraction, is not a predictor of RID or RICV. Separate delineation of the aforementioned critical structures, as well as others, may better identify dose tolerances to maintain function and further prioritize the importance of structures in RID and RICV.
PMID: 24123019
ISSN: 0250-7005
CID: 1261582

Present status and future directions of intraoperative radiotherapy

Debenham, Brock J; Hu, Kenneth S; Harrison, Louis B
In this Review, we summarise recent published work on the use of intraoperative radiotherapy to treat common tumour sites in the primary or recurrent setting. Techniques, radiobiology, and the physics of intraoperative radiotherapy are also explored. Disease sites discussed in this Review include head and neck cancer, breast cancer, sarcoma, gastrointestinal cancer, genitourinary cancer, gynaecological cancer, thoracic cancer, and palliative applications.
PMID: 24079873
ISSN: 1470-2045
CID: 1499042

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Orhi, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gamez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B
OBJECTIVES: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS: We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.
PMID: 23623404
ISSN: 1368-8375
CID: 1499052