Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers-A Preclinical Study in a Porcine Model.

OBJECTIVE: We have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. METHODS: This study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. RESULTS: No adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. CONCLUSIONS: In this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

Using 3-D-Printed Structures to Evaluate the Potential Causes of the Color Doppler Twinkling Signature.

OBJECTIVE: The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation occurring on rough objects such as kidney stones, some breast biopsy clips, catheter guidewires and sandpaper. The objective was to investigate the correlation between the surface characteristics of helical constructs with different groove geometries and the occurrence of twinkling, as well as to identify locations conducive to bubble retention and/or cavitation. METHODS: Six half-cylinders were created with a microscale 3-D printer with 5 µm resolution to replicate the geometry of twinkling helical constructs resembling catheter guidewires. Four copies of each marker including a non-twinkling control were printed. The half-cylinders had pitch (peak-to-peak distance) values ranging from 87.5 to 343 µm and amplitude (groove depth) values ranging from 41.5 to 209 µm. The half-cylinders were submerged in degassed water and optically imaged before and after ultrasound insonification to visualize bubbles on the cylinders. The cylinders remained submerged while scanning with the color Doppler mode at frequencies from 3.1 to 6.3 MHz using a GE Logiq E9 scanner and 9L linear array transducer. RESULTS: Two markers exhibited twinkling: one with pitch-to-amplitude ratio of 174/210 µm/µm (0.8) that twinkled only with pre-existing bubbles on the marker; the other had a ratio of 87/87 µm/µm (1.00) that twinkled without pre-existing bubbles on the marker. CONCLUSION: This work provides strong evidence that both existing bubbles and either cavitation or ultrasound wave interactions with patterned or rough surfaces are significant factors in producing the twinkling signature.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Evaluation of Robustness of Local Phase Velocity Imaging in Homogenous Tissue-Mimicking Phantoms.

Shear wave elastography (SWE) is a method of evaluating mechanical properties of soft tissues. Most current implementations of SWE report the group velocity for shear wave velocity, which assumes an elastic, isotropic, homogenous and incompressible tissue. Local phase velocity imaging (LPVI) is a novel method of phase velocity reconstruction that allows for accurate evaluation of shear wave velocity at specified frequencies. This method's robustness was evaluated in 11 elastic and 8 viscoelastic phantoms using linear and curvilinear arrays. We acquired data with acoustic radiation force push beams with different focal depths and F-numbers and reconstructed phase velocity images over a wide range of frequencies. Regardless of phantom, push beam focal depth and reconstruction frequency, an F-number around 3.0 was found to produce the largest usable area in the phase velocity reconstructions. For elastic phantoms scanned with a linear array, the optimal focal depth, frequency range and maximum region of interest (ROI) were 20-30 mm, 100-400 Hz and 2.70 cm2, respectively. For viscoelastic phantoms scanned with a linear array, the optimal focal depth, frequency and maximum ROI were 20-30 mm, 100-300 Hz and 1.54 cm2, respectively. For the curvilinear array in the same phantoms, optimal focal depth, frequency range and maximum ROIs were 45-60 mm, 100-400 and 100-300 Hz and 1.54 cm2, respectively. In further work, LPVI reconstructions from inclusion phantoms will be evaluated to simulate non-homogeneous tissues. Additionally, LPVI will be evaluated in larger-volume phantoms to account for wave reflection from the containers when using the curvilinear array.

Detecting Kidney Stones Using Twinkling Artifacts: Survey of Kidney Stones with Varying Composition and Size.

In recent years, work has been done to understand the mechanisms of Doppler ultrasound twinkling artifacts (TAs) and why they appear over kidney stones. In the work described here, twinkling artifacts were evaluated as a possible method of locating and characterizing kidney stones. Doppler ultrasound scanning was used to evaluate 47 stones of different types and sizes in the range 1.31-55.76 mm2 in cross-sectional area (average = 9.65 mm2). An isolated stone study was used to understand the behavior of the TAs. An ex vivo kidney study was conducted to determine if the renal tissue impeded localization of the TAs to the stones. An ex vivo study of randomly placed stones was used to evaluate the robustness of the method for detecting stones that were placed by an independent party. The TAs were found to be qualitatively consistent in appearance across stone types, sizes and scanning parameters in the isolated stone study. Quantitative assessment of TA amplitude for isolated stones was also found to be consistent for each class of stones across multiple days. The TAs were also found to be isolated to the stone when placed in an ex vivo kidney. The study of randomly placed stones revealed that this method could find all 47 stones used in a clinical situation with only two false positives. A few limitations to this method were noted involving accurate sizing of stones and the specificity of characterizing the stones. Further work will be done to overcome limitations by improving the Doppler acquisition and processing code, as well as by evaluating the use of TAs in human studies.

Attenuation Measuring Ultrasound Shearwave Elastography as a Method for Evaluating Pancreatic Viscoelasticity.

Pancreatic cancer is the fourth most common cause of cancer-related fatalities as there are a limited number of tools to diagnose this disease in its early stages. Pancreatitis is characterized as an inflammation of the pancreatic tissue due to an excess amount of pancreatic enzymes remaining in the organ. Both of these diseases result in a stiffening of the tissue which makes them suitable for the use of elastography techniques as a diagnostic method. However, these methods typically assume that the tissue is purely elastic when biological tissue is inherently viscoelastic. The attenuation measuring ultrasound shear elastography (AMUSE) method, which measures both attenuation and shear wave velocity was used to characterize the viscoelasticity of pancreatic tissue. This method was tested in ex vivo normal porcine samples that were also stiffened in formalin and in vivo by conducting studies in healthy human subjects. Ex vivo testing showed ranges of phase velocity, group velocity, and phase attenuation values of 1.05 - 1.33 m/s, 0.83 - 1.12 m/s, and 183 - 210 Np/m. After immersing the ex vivo tissue in formalin there was a distinguishable difference between normal and stiffened tissue. This study produced percent difference ranges of phase velocity, group velocity, and phase attenuation from 0 to 100 minutes in formalin of 30.0% - 56.5%, 38.2% - 58.6%, and 55.8% - 64.8%, respectively. The ranges of phase velocity, group velocity, and phase attenuation results in human subjects were 1.53 - 1.60 m/s, 1.76 - 1.91 m/s, and 196 - 204 Np/m, respectively. These results were within a similar range reported by other elastography techniques. Further work with the AMUSE method in subjects with pancreatitis and cancer is needed to determine its effectiveness in showing a difference between healthy and diseased tissue in humans.

Randomized phase III study of 2 cisplatin-based chemoradiation regimens in locally advanced head and neck squamous cell carcinoma: impact of changing disease epidemiology on contemporary trial design.

BACKGROUND: Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens. METHODS: Patients with locally advanced HNSCC were treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100 mg/m(2) on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m(2) /day) and 5-fluorouracil (5-FU; 1000 mg/m(2) /day) continuous 96-hour infusions on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS). RESULTS: Between February 2008 and October 2011, 69 patients were enrolled in this study. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. Eighty-three percent of patients had oropharyngeal cancer, of these, 86% were human papillomavirus (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41 months) for arms A and B were: RFS 87% versus 80% (p = .24), overall survival 97% versus 85% (p = .013), locoregional control 96% versus 94% (p = .52), and distant metastatic control 91% versus 87% (p = .9). CONCLUSION: Multiagent was not superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes.

Cervical sympathetic chain paraganglioma: a report of 2 cases and a literature review.

We review 2 cases of surgically and pathologically confirmed paraganglioma of the cervical sympathetic chain. Both patients-a 46-year-old man and a 33-year-old woman-were treated surgically. Intraoperatively, both tumors were found to be hypervascular and arising from the cervical sympathetic chain. Histopathologic analysis confirmed both as paragangliomas. Paragangliomas arising from the cervical sympathetic chain are exceptionally rare, but they must be considered in the differential diagnosis of parapharyngeal masses. They often present with ipsilateral Horner syndrome and oropharyngeal fullness, and they may be associated with a higher rate of catecholamine secretion. Typical imaging characteristics include anterolateral or lateral displacement of both the carotid and jugular vessels.

Patient reported outcomes in endoscopic and open transcervical treatment for Zenker's diverticulum.

OBJECTIVES/HYPOTHESIS: To compare long-term symptomatic outcomes between external transcervical (ET) and endoscopic stapling diverticulotomy (ESD) surgeries for Zenker's diverticulum. STUDY DESIGN: Retrospective review. METHODS: Patients undergoing surgery for Zenker's diverticulum surgery between 1998 and 2010 with at least 1 year follow-up were telephoned and questioned for dysphagia, choking, regurgitation, and halitosis based on a validated Gastrointestinal Quality-of-Life Index. Symptom degree preoperatively and at phone call was assessed. Patients rated their overall postoperative symptoms as worsened, unchanged, improved, or completely resolved. RESULTS: A total of 96 patients were eligible for inclusion and 55 were successfully contacted. Of these, 24 underwent ESD and 31 had ET operations. Average follow-up time was significantly longer for the ET group than the ESD group (5.7 vs. 3.1 years respectively, P < 0.01). Gender, age at operation, diverticulum size, and preoperative symptom scores were not statistically different between the two groups. For both techniques, symptom scores showed significant improvement postoperatively (P < 0.01). A greater proportion of patients undergoing ET procedures reported their symptoms to be completely resolved or improved compared with the ESD group (93% vs. 67%, P = 0.015). Patients undergoing ET demonstrated a greater change or improvement in survey score compared to ESD patients (7.23 vs. 3.42, P = 0.014). CONCLUSION: Both the ET and ESD surgeries significantly benefit patients, regardless of diverticulum size. Long-term symptomatic outcomes between the two populations indicate that patients with ET procedures attain a greater degree of resolution of preoperative symptoms.

Single-arm phase II study of multiagent concurrent chemoradiotherapy and gefitinib in locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC). METHODS: Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib. RESULTS: Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts. CONCLUSIONS: Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity.

Multi-agent concurrent chemoradiotherapy for locally advanced head and neck squamous cell cancer in the elderly.

BACKGROUND: The reported decreasing benefit with increasing age from concurrent chemoradiotherapy in head and neck cancer patients prompted this retrospective review. METHODS: Two courses of cisplatin-based concurrent chemoradiotherapy were given to fit patients ≥70 years with locoregionally advanced cancers. Clinical characteristics, treatment, and outcomes were compared with those for an identically treated cohort <70 years. RESULTS: There were 44 patients ≥70 and 137 patients <70 years. Clinical characteristics, treatment and toxicities were similar except that the elderly were less likely to receive both chemotherapy courses, experienced more myelosuppression, required more unplanned hospitalization, and were feeding-tube dependent longer. Projected 5-year disease-specific survival (71% vs 74%) and freedom from recurrence (69% v. 71%) were nearly identical. CONCLUSIONS: Although these selected elderly patients experienced greater myelosuppression and supportive care requirements, outcomes were the same as in younger patients. Age alone should not be considered a contraindication to aggressive chemoradiotherapy for this disease.

Extent of neck dissection required after concurrent chemoradiation for stage IV head and neck squamous cell carcinoma.

BACKGROUND: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate. METHODS: A retrospective chart review of neck management in patients after chemoradiation was performed. RESULTS: Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery. Patients were pathologically positive 13.8% and 39.6% of the time after clinical complete or partial response, respectively. Regional recurrence was more frequent in necks with partial clinical (p = .04) or pathologic responses (p < .01) and with primary site recurrences (p < .01). CONCLUSIONS: It is still safest at our institution to perform selective neck dissection on patients with > or = N2 neck disease when initially observed to prevent unsalvageable regional recurrence until more accurate interval assessment tools are confirmed.

Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy.

BACKGROUND: Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. METHODS: Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. RESULTS: The 5-year Kaplan-Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. CONCLUSION: Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective.

Ability of positron emission tomography to detect residual neck node disease in patients with head and neck squamous cell carcinoma after definitive chemoradiotherapy.

OBJECTIVE: To report our experience using the neck examination, computed tomography (CT), and positron emission tomography (PET) to clinically evaluate node-positive patients with head and neck squamous cell cancer for residual neck node disease after definitive chemoradiotherapy. DESIGN: Retrospective review of all Cleveland Clinic patients with head and neck squamous cell cancer and N2 or N3 neck node involvement at presentation who were treated with definitive concurrent chemoradiotherapy and who underwent clinical restaging after treatment using the neck examination, CT, and PET. SETTING: Tertiary care referral institution. PATIENTS: Forty-eight patients with 72 positive necks at diagnosis were followed up for a median of 20 months. MAIN OUTCOME MEASURES: Palpable nodes on examination, nodes larger than 1 cm, nodes with central necrosis on CT, or any hypermetabolic lymph nodes on PET were considered clinical evidence of residual nodal disease. The true rate of pathologic involvement was determined by histologic examination after planned neck dissection or if regional recurrence developed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 3 clinical assessment tools. RESULTS: Planned neck dissection was performed in 33 necks and was positive for residual neck node disease in 5 necks. A delayed neck dissection was performed in 5 necks and was positive in 3 necks. The positive predictive value was low for all 3 clinical assessment tools. The addition of PET did not significantly improve the negative predictive value or positive predictive value of CT and the clinical examination. CONCLUSIONS: Residual neck node disease after definitive chemoradiotherapy was infrequent and was not well predicted by PET. A positive PET finding in this setting is of little utility. Although a negative PET finding was highly predictive for control of neck disease after chemoradiotherapy, it added little to the clinical neck examination and CT.

Risk factors for hypopharyngeal/upper esophageal stricture formation after concurrent chemoradiation.

BACKGROUND: Concurrent chemoradiation therapy has been demonstrated to be effective as an organ-sparing treatment for select advanced head and neck squamous cell carcinoma (HNSCC). However, this treatment modality is not without side effects. One side effect is the formation of upper esophageal strictures. As concurrent chemoradiation treatment is used more frequently, it is important to identify risk factors associated with stricture formation. METHODS: A retrospective chart review of all patients who had undergone definitive concurrent chemoradiation treatment between 1989 and 2002 was performed. Exclusion criteria included death within 1 year or persistent/recurrent disease that required surgical salvage at the primary site. The outcome measure was stricture formation as determined by both objective findings (barium swallow or endoscopy) and the need for dilation after treatment. RESULTS: Of the 222 patients in this cohort, there were enough data for 199 patients to assess for stricture formation. Strictures developed in a total of 41 patients (21%). Significant predictive factors were a twice-daily (BID) radiation fractionation (p = .007), female sex (p = .015), and a hypopharyngeal primary site (p = .01). Age and tumor extent were not significant factors in stricture formation (p = .15 and p = .23, respectively). CONCLUSIONS: Symptomatic strictures occur in 21% of patients undergoing concurrent chemoradiation for HNSCC. Female sex, BID radiation fractionation, and a hypopharyngeal primary site are significant predictive factors for stricture formation.

Multiagent concurrent chemoradiotherapy for locoregionally advanced squamous cell head and neck cancer: mature results from a single institution.

PURPOSE: A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer. PATIENTS AND METHODS: Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease. RESULTS: With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors. CONCLUSION: Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.

Does acid suppressive therapy reduce the risk of laryngeal cancer recurrence?

OBJECTIVE/HYPOTHESIS: Gastroesophageal reflux disease (GERD) is implicated in laryngeal cancer pathogenesis and recurrence posttherapy. There are currently limited data on the effect of acid suppressive therapy in decreasing the recurrence of laryngeal cancer. Therefore, we conducted this study to identify potential effect of GERD and acid suppressive therapy on recurrences after larynx-preserving therapies. STUDY DESIGN: Case control study. METHODS: Cases and controls, derived from a single tertiary care center, were patients who had newly diagnosed localized laryngeal cancer (T3 or less and absence of nodes) and having undergone larynx-preserving surgery or radiotherapy/chemotherapy were followed between January 1, 2000 and December 31, 2003. Univariable associations were performed for demographics, smoking and alcohol patterns, stage of tumor, initial treatment, surgeon of record, presence of GERD, and the use of acid suppressive medications. Multivariable associations were performed for clinically significant variables. RESULTS: Of 258 patients with laryngeal cancer, 61 satisfied the selection criteria. Twenty-two of 61 (36%) developed recurrence and constituted cases, whereas 39/61 (64%) did not have recurrence and constituted controls. On univariable analysis, significant factors for decreased recurrences were GERD, hazard ratio 0.24 (95% confidence interval [CI] 0.08-0.71), and acid suppressive therapy, hazards 0.22 (95% CI 0.07-0.66). On multivariable analysis, laryngeal cancer recurrence was significantly less in those on acid suppressive therapy, hazard 0.31 (95% CI 0.13-0.75). CONCLUSIONS: Acid suppression postlaryngeal cancer therapies may have protective effect on laryngeal cancer recurrences. A prospective study is needed to better define this perceived beneficial effect.

Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?

BACKGROUND: The role of neck dissection (ND) after definitive chemoradiotherapy for squamous cell head and neck cancer is incompletely defined. We retrospectively reviewed 109 patients with N2-N3 disease treated with chemoradiotherapy to identify predictors of a clinical complete response in the neck (CCR-neck), pathologic complete response after ND (PCR-neck), and regional failure. METHOD: All patients were given 4-day continuous infusions of 5-fluorouracil (1000 mg/m2/d) and cisplatin (20 mg/m2/d) during the first and fourth weeks of either once daily (n = 68) or twice daily (n = 41) radiation therapy. ND was considered for all patients after completion of chemoradiotherapy and was performed in 32 of the 65 patients achieving a CCR-neck after chemoradiotherapy and in all 44 patients with residual clinical evidence of neck disease. CCR-neck, PCR-neck, and regional failure were then correlated with potential predictors, including T, N, largest lymph node size (<3 cm, > or =3 cm), primary tumor site, and radiation fractionation schedule. RESULTS: Achievement of a CCR-neck was predicted by N, N2 vs N3 (53 of 80 vs 12 of 29, p =.019) and by largest lymph node size, <3 cm vs > or =3 cm (19 of 25 vs 46 of 84, p =.06). Achievement of a PCR-neck could not be predicted by any clinical parameter. Regional failure occurred both in patients undergoing ND and those not dissected (5 of 76 vs 4 of 33, p =.33) and proved more likely only in the ND patients with residual positive pathology compared with those achieving a PCR-neck (5 of 25 vs 0 of 51, p <.001). Primary site was not a useful predictor of CCR-neck, PCR-neck, or regional failure. Most importantly, CCR-neck (vs

Recurrent head-and-neck chemodectomas: a comparison of surgical and radiotherapeutic results.

PURPOSE: To compare the outcome of salvage radiotherapy (RT) and surgery for recurrent head-and-neck chemodectomas. MATERIALS AND METHODS: We retrospectively studied 70 patients with benign chemodectomas of the head and neck treated with surgery at the Cleveland Clinic between July 1969 and August 1999; 29 of these patients were diagnosed with recurrent tumors. Salvage RT was used in 12 patients (gamma knife radiosurgery for 7, conventional external beam RT for 4, and intensity-modulated RT for 1 patient). The median follow-up was 55 months for the entire group of 70 patients. RESULTS: The median time to recurrence was 36 months. Of the recurrences, 16 were glomus jugulare, 7 were carotid body tumors, 5 were glomus tympanicum, and 1 was thyroid paraganglioma. RT was used in 12 patients (9 patients with glomus jugulare, 2 with glomus tympanicum, and 1 with thyroid paraganglioma). Surgery was performed in 17 patients (7 patients with glomus jugulare, 7 with carotid body, and 3 with glomus tympanicum). For patients with glomus jugulare and glomus tympanicum tumors, the 5-year freedom from disease progression was 100% for patients treated with RT vs. 62% for those treated with surgery (p = 0.0124). Seven patients with carotid body tumors and 1 patient with thyroid paraganglioma were treated successfully with surgery and RT, respectively. No significant side effects were associated with RT; however, postoperative complications occurred in 8 of the 17 surgery patients (new cranial nerve palsies, meningitis, infection, and cerebrospinal fluid leak). CONCLUSION: Salvage RT appears superior to surgery and should be considered the treatment of choice for patients with recurrent glomus jugulare and glomus tympanicum tumors. For recurrent carotid body tumors, surgery produced excellent local control, most likely because of the easier resectability in this location.

Maximizing local control and organ preservation in stage IV squamous cell head and neck cancer With hyperfractionated radiation and concurrent chemotherapy.

PURPOSE: Results are reported from an aggressive chemoradiotherapy protocol for advanced squamous cell head and neck cancer. PATIENTS AND METHODS: Patients with advanced squamous cell head and neck cancer were treated with hyperfractionated radiation therapy (72 Gy at 1.2 Gy twice per day) and two courses of concurrent chemotherapy with fluorouracil (1,000 mg/m(2)/d) and cisplatin (20 mg/m(2)/d), both given as 96-hour continuous intravenous infusions during weeks 1 and 4 of radiation therapy. Primary-site resection was reserved for residual or recurrent primary-site disease after chemoradiotherapy. Neck dissection was considered for N2 or greater disease, irrespective of clinical response, and for residual or recurrent neck disease after nonoperative treatment. RESULTS: Forty-one patients with stage IV disease were treated. Toxicity was significant, with grade 3 to 4 mucositis in 98%, dysphagia in 88%, and skin reaction in 85%. Neutropenic fever requiring hospitalization occurred in 51%. Despite feeding tube placement in 35 patients (85%), the mean weight loss during chemoradiotherapy was 13.3% of initial body weight. One patient died during treatment as a result of a pulmonary embolus. At a median follow-up period of 30 months, the 3-year Kaplan-Meier projected overall survival was 59%, disease-specific survival 69%, likelihood of local control without surgical resection 91%, and local control with surgical resection 97%. The likelihood of distant disease control at 3 years was 74%, and distant metastases were present in eight of 13 patients who died. CONCLUSION: This chemoradiotherapy schedule produces considerable but manageable toxicity. Survival and organ preservation are excellent for this poor-prognosis patient cohort. Distant metastases are the most common cause of treatment failure.