Patients Underwent Salvage Surgery Research Articles

Minimizing complications in salvage head and neck oncological surgery following radiotherapy and chemo-radiotherapy

The term salvage surgery denotes oncological surgery after failed radiotherapy or chemoradiotherapy (CRT). Salvage surgery is a high-risk endeavour as it carries a significant risk of complications. The purpose of this review is to assess the ways in which complications from salvage surgery can be prevented and minimized. This is a complex subject and complications are often multifactorial and interrelated. There are many aspects that can be discussed; however, to address each of them individually would be impossible and beyond the scope of this article. We will, therefore, focus this review on the most relevant aspects to current practice for head and neck surgeons. Salvage surgery after failure of radiotherapy and CRT remains controversial and many aspects still lack evidence. Many patients with recurrent cancer are not suitable for salvage surgery due to severe co-morbidities or disease progression. Salvage surgery is best carried out in tertiary centres by experienced multidisciplinary teams. Preoperative assessment and evaluation is critical to success and to minimize complications. Surgical principles include single incisions, delicate tissue handling, use of frozen sections, adopting a critical approach to neck dissections and the use of flaps, secondary surgical voice restoration for laryngectomies and appropriate postoperative care. This review emphasizes the importance of a multidisciplinary approach by experienced teams, the centralization of resources and teams, a structured and thorough patient assessment, surgical planning and a systematic attention to detail when addressing patients undergoing salvage surgery.

Evaluation of 18F-FDG PET/CT and CT/MRI with Histopathologic Correlation in Patients Undergoing Salvage Surgery for Head and Neck Squamous Cell Carcinoma

(18)F-fludeoxyglucose (FDG) positron emission tomography (PET) is a sensitive and specific method for detecting active residual disease after chemoradiotherapy or radiotherapy, but few studies have accurately evaluated its diagnostic accuracy with histopathologic correlation. We therefore investigated the clinical utility of (18)F-FDG PET/computed tomography (CT) in patients undergoing salvage surgery for residual head and neck squamous cell carcinoma (HNSCC) after primary nonsurgical treatments. Thirty-nine patients who initially received chemotherapy (n=23), radiotherapy (n=3), or chemoradiotherapy (n=13) were evaluated 8-28weeks later by (18)F-FDG PET/CT and CT/magnetic resonance imaging (MRI) prior to salvage surgery to clear residual disease. These results were compared with those of histopathologic analysis of the primary tumor and neck dissection tissue samples. Of these 39 patients, 22 (56%) had residual primary tumor. The sensitivity, specificity and accuracy of (18)F-FDG PET/CT for detecting primary tumors were 91, 65, and 79%, respectively. Of 56 dissected heminecks, 37 (66%) had residual metastatic lymph nodes. (18)F-FDG PET/CT and CT/MRI had accuracies for positive heminecks of 91 and 75%, respectively (P=0.004). On a cervical level-by-level-based analysis, (18)F-FDG PET/CT and CT/MRI had accuracies of 89 and 78%, respectively (P<0.001); (18)F-FDG PET/CT had a specificity of 93% and a negative-predictive value of 92% for detection of positive levels. (18)F-FDG PET/CT is superior to CT/MRI in detecting residual nodal disease in head and neck squamous cell carcinoma patients undergoing salvage surgery. Accurate preoperative diagnosis using (18)F-FDG PET/CT may help to determine the extent of salvage surgery.

Secondary Skull Base Malignancies in Survivors of Retinoblastoma: The Memorial Sloan Kettering Cancer Center Experience

We report the pathology and outcome of secondary skull base tumors in patients previously treated with external beam radiation for retinoblastoma (Rb). Rb patients are at increased risk of second head and neck primary malignancies due to early radiation exposure during treatment and loss of RB1 protein in genetic carriers. An institutional database was reviewed for patients with retinoblastoma who had previously received radiation therapy and subsequently developed skull base tumors. Seventeen patients met the selection criteria. The median age of Rb diagnosis was 12 months. Thirteen cases underwent enucleation in addition to radiation therapy as part of initial Rb treatment. A median of 19 years elapsed between the diagnosis of Rb and diagnosis of skull base malignancy. The most common tumors were osteogenic sarcoma (39%) and leiomyosarcoma (22%). Eleven (71%) patients received postoperative chemotherapy, and 7 (41%) received postoperative radiotherapy. Three (24%) patients underwent salvage surgery for recurrent disease. Five-year survival was 68%, and 10-year survival was 51% by Kaplan-Meier analysis. Secondary malignancy in Rb patients is a well-defined event. The use of surgery with appropriate adjuvant therapy was associated with a 51% 10-year survival in this study population.

Salvage surgery after failure of non surgical therapy for advanced head and neck cancer

Introduction: for organ and function preservation, chemoradiotherapy is gaining popularity for primary treatment of advanced head and neck cancer, re- serveing surgery for salvage. Methods: Retrospective outcome analysis to determine the results of salvage surgery after failure of primary treatment of advan- ced head and neck cancer by chemoradiotherapy. 104 patients with advanced head and cancer were initially treated by chemoradiotherapy. Follow-up was evalu- ated in 27 patients undergoing salvage surgery for re- current tumor (larynx n = 13; oral cavity n = 9; hypo- pharynx n = 5). The initial tumor is stage T3 in 11 cases and T4 in 16 cases. 10 patients had primary tumors stage III and 17 patients had tumors stage IV. Results: One postoperative death occured following surgery. The overall incidence of complications was 9/ 27 (%). Recurrent disease developed at the primary initially treated in 25 cases and in the neck in 2 cases after a mean follow-up of 11 months (3 - 136 months). After salvage surgery, loco-regional recurrence and/ or distant disease developed in 10/27 patients after a mean follow-up of 4 months. 6/10 (60%) patients died after re-recurrence despite salvage chemotherapy. Conclusion: Salvage surgery after failure of initial chemoradiotherapy is burdened with high morbi- dity and bad oncological outcome. We demonstrated that it is difficult to salvage locally recurrent head and neck cancer especially at more advanced T-stages or when tumor recur. The limited effect of surgical salvage for recurrent tumor need to be addressed when choosing the initial treatment plan.

Salvage Surgery After Stereotactic Radiotherapy: A New Challenge for Thoracic Surgeons

Although no large randomized trials are available comparing surgery with radiotherapy for early-stage non-small cell lung cancer (NSCLC), surgical resection is the preferred treatment in functionally operable patients. Stereotactic radiotherapy (SRT), precisely delivering a high local radiation dose, has emerged as a new treatment modality to completely eradicate the primary tumor. In this way, SRT, sometimes also called stereotactic radiosurgery, could be considered equivalent to surgical resection, although there is currently no evidence to prove that this presumption is true. SRT has been mostly applied in patients with NSCLC and severe comorbidity precluding surgical resection, although recently, functionally operable patients also have been included, and indications have expanded to pulmonary oligometastatic disease. Frequently, after a variable follow-up time, local recurrences will be detected. Thoracic surgeons are currently confronted with a new challenge: is so-called salvage surgery feasible after high-dose SRT, are more technical difficulties encountered during the intervention, and should a higher postoperative morbidity be anticipated? Will there be an increased incidence of prolonged air leaks, bronchopleural fistulas, or empyemas when operating on friable lung tissue with decreased bronchial vascularization? Two reports, both originating from Japan, in the current issue deal with this topic. In the article by Chen et al., 1 144 patients undergoing SRT during a 10-year period for a peripherally located NSCLC were retrospectively evaluated. A biologic effective dose of 105.6 Gy was reached. After a median follow-up of 31.5 months, local recurrence was detected in 24 patients (16.7%). Although all patients were initially operable, only five (20.8%) underwent salvage surgical resection, the other patients being treated by chemotherapy, chemoradiation, or best supportive care. Lobectomy with systematic nodal dissection was found to be feasible in these five patients without major technical difficulties or increased postoperative morbidity. Pathologic stage I was found in these five patients with a tumor size ranging from 25 to 50 mm. Recurrent disease was mostly found in the central portion of the irradiated area. The second article by Neri et al., 2 which is also a retrospective study, describes surgical salvage in seven patients who underwent SRT for stage I NSCLC or lung metastases. The initial group comprised 81 patients with stage I disease and 46 patients with lung metastases who had a total of 65 metastatic lesions. Local recurrence was detected in 18 patients (14.1%), 6 with stage I lung cancer and 12 with lung metastases. Less than 50% of these patients underwent salvage surgery: only two with stage I disease and five with pulmonary metastases. The median period of local control was only 9 months, and the median period between SRT and salvage lung resection was 10 months. Six patients underwent lobectomy and one segmentectomy with apparently no technical difficulties. However, in two patients, a complete resection could not be obtained. Postoperatively, one patient suffered from a pulmonary fistula, and in four patients, postradiotherapy pneumonitis was encountered.

Vascularized Free Tissue Transfer for Reconstruction of Ablative Defects in Oral and Oropharyngeal Cancer Patients Undergoing Salvage Surgery Following Concomitant Chemoradiation

Statement of the Problem: Contemporary emphasis on organ preservation utilizing chemoradiotherapy protocols for the treatment of laryngeal, hypopharyngeal, and oropharyngeal squamous cell carcinoma, as well as increasing enthusiasm for adjuvant, concomitant chemoradiation for surgically resectable, advanced stage oral squamous cell carcinoma, underscores the evolving role and increased importance of free tissue transfer in irradiated fields. The addition of chemotherapy, which has been shown to improve survival in advanced head and neck cancer, intensifies the effect of radiation on the surrounding tissue and can impact wound healing.

Salvage surgery after locoregional failure in head and neck carcinoma patients treated with chemoradiotherapy

With the increasing use of concomitant chemoradiotherapy (CCRT) in the treatment of advanced head and neck carcinoma, surgery has lost ground as the first therapy and is reserved as a salvage treatment in cases of locoregional failure. The objective of our study was to review our experience in patients who had a local or regional recurrence after treatment with CCRT. Thirty-two patients underwent salvage surgery after CCRT: 24 were treated with a local or locoregional resection and 8 patients with a neck dissection only. In patients who had surgery involving the primary location of the tumor, some kind of reconstruction was required in 83% of cases. One or more postoperative complications occurred in nine patients. The median hospital stay was 18.5 days. There was a significant difference in hospital stay in relation to the appearance of surgical complications. Five-year adjusted survival after salvage surgery was 34.2% (CI 95% 13.2-55.2%). Adjusted survival was related to the status of the resection margins and appearance of neck nodes with extracapsular spread in the neck dissection. In conclusion, salvage surgery after CCRT involves extensive resections, requiring reconstruction techniques with regional or microanastomosed free flaps in most cases, achieving acceptable outcomes.

Complicated Surgical Resection of Malignant Tumors in the Upper Cervical Spine After Failed Ion-Beam Radiation Therapy

Case report. To report 3 cases of malignant tumors in the upper cervical spine that were treated surgically by a combination of posterior tumor resection and stabilization and anterior tumor resection through a mandible-splitting approach after failed ion-beam radiation therapy. Few clinical reports have described in detail the postoperative complications associated with transoral surgical resection of tumors in the upper cervical spine after unsuccessful ion-beam radiation therapy. Three patients with malignant tumors in the upper cervical spine who had undergone ion-beam radiotherapy and experienced tumor recurrence were treated by a combination of posterior and anterior surgery through a mandible-splitting approach. One patient (patient 1, a 32-year-old man) had a hemangioendothelioma at the C2 and C3 level, whereas the other 2 patients (patient 2, a 66-year-old woman and patient 3, a 65-year-old man) had a chordoma at the C2 and C3 level. The intralesional but macroscopic total resection of the tumors was achieved in all 3 patients. However, serious complications developed after surgery, including deep wound infection, cerebrospinal fluid leakage, and meningitis in patient 1, prolonged swallowing difficulty, subsidence of the strut graft, and recurrence in patient 2, and deep wound infection and discitis causing progressive paralysis in patient 3. All patients underwent salvage surgery, including debridement of the wound in patient 1, posterior reinforcement using instrumentation and posterior tumor resection for the recurrent tumor in patient 2, and anterior debridement of the wound with a pedicle flap using the pectoral major muscle in patient 3 to address these problems. Patients 1 and 3 had no signs of recurrence at the time of a follow-up examination. Severe complications, mainly associated with the disturbance in healing of the retropharyngeal wall, were observed in all 3 patients. A preventive method, such as primary repair of the retropharyngeal wall using muscular/musculocutaneous flaps, should be considered for patients undergoing resection through a transoral approach after ion-beam irradiation.

Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72 Gy (range, 62-76 Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

Outcomes of salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal cancer

To evaluate outcomes of salvage surgery with free flap reconstruction for recurrent squamous cell carcinoma of the oropharynx and oral cavity with increased use of chemoradiotherapy. Retrospective patient review. All patients undergoing salvage surgery with free flap reconstruction for oropharynx (n = 36) and oral cavity (n = 36) squamous cell carcinomas between January 2001 and January 2008 were obtained. Mean follow-up was 14 months. Previous chemoradiotherapy was used in 40% and radiotherapy alone in 60%. Complications were more frequent in oropharynx than oral cavity tumors (36% and 14%, respectively; P = .05) requiring more secondary procedures (15 for oropharynx vs. six for oral cavity). Few patients returned to a normal diet (8%), and a majority retained an enterogastric feeding tube (56%). Median survival overall following salvage surgery was 44.8 months for oral cavity and 53.8 months for oropharynx head and neck squamous cell carcinoma. Overall estimated 1-, 2-, and 5-year observed survivals were 98%, 77.2%, and 43.7%, respectively. Twelve patients had a disease-free interval of <6 months, 92% of whom died of disease. Of 17 patients with disease at the primary site and involved regional lymph nodes, 94% died of disease. Salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal tumors after chemoradiotherapy has acceptable morbidity and similar cure rates as salvage following radiotherapy without chemotherapy. Concurrent nodal recurrence and short disease-free interval are associated with reduced cure rates. A significant proportion will require enterogastric feeding and few will tolerate a normal diet.

The assessment of pharyngocutaneous fistula rate in patients treated primarily with definitive radiotherapy followed by salvage surgery of the larynx and hypopharynx

To determine whether definitive radiotherapy prior to surgery increases the rate of pharyngocutaneous fistula (PCF) following laryngectomy or hypopharyngectomy and to determine if differences in duration of time between definitive radiotherapy and surgery alters PCF rate. A retrospective review of 152 patients treated surgically for primary laryngeal or hypopharyngeal squamous cell carcinoma. Following previous definitive radiotherapy treatment 38 patients underwent salvage surgery and 114 patients underwent primary surgery with curative intent. The PCF rate was assessed in both groups. The rate of PCF was found to be significantly higher in the salvage surgery group than those undergoing primary surgery (34.2% vs. 15.7%) (P < .05). Fistula rate was also higher in the subgroup that received concurrent chemoradiation to radiotherapy alone (P = .002). The patients who developed PCF in the salvage surgery group had significantly lower median time to surgery (5.8 months) than the nonfistula group (9.8 months) (P = .032). PCF rate was 75% within 4 months of radiotherapy to salvage surgery compared to 25% after 4 months (P = .034). Within 12 months of radiotherapy this percentage was 48% compared to 0% after 12 months (P = .014). The median radiotherapy dose was significantly higher in those whose surgery was complicated by PCF (70 Gy) compared to patients who did not develop a fistula (64 Gy) (P = .001). Patients undergoing salvage surgery within 12 months, and in particular within 4 months, who have received high dose radiotherapy (>64 Gy) or concurrent chemoradiation are at high risk of developing PCF.

Salvage surgery after concomitant chemoradiation in head and neck squamous cell carcinomas—Stratification for postsalvage survival

Salvage surgery after concomitant chemoradiation therapy (CCRT) for patients with head and neck squamous cell carcinomas (HNSCC) is challenging because of its associated morbidity/mortality and the poor prognoses of these patients. The outcome analysis of prospectively collected data from 93 patients with HNSCC with local and/or regional shows treatment failures but without distant metastasis after CCRT. Thirty-eight patients underwent salvage surgery, whereas 55 underwent palliative treatment, with 2-year overall survival rates of 43.4% and 0%, respectively. Initial stage IV tumors (p = .017) and concurrent local and regional failures (p = .003) were independent predictors for decreased survival after salvage surgery. Two-year overall survival rates for patients with 2, 1, or none of these predictive factors were 0%, 49%, and 83%, respectively (p = .0005). Salvage surgery after CCRT has acceptable outcomes. Initial stage IV tumors and concurrent local and regional failures were independent predictors that can stratify patients into distinct prognostic groups for postsalvage survival.

Salvage surgery after induction chemotherapy with paclitaxel/cisplatin and primary radiotherapy for advanced laryngeal and hypopharyngeal carcinomas

Induction chemotherapy followed by primary radiotherapy in responders is considered an alternative to surgery for advanced cancer of the larynx and hypopharynx (LHC). Comparison of therapeutic approaches is challenging and must respect oncological and functional outcome as well as quality of life during and after treatment. One aspect of primary radiochemotherapy is the option of salvage surgery in case of residual tumor. The outcome after salvage surgery following new organ-preserving strategies has to be examined. All patients undergoing induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy from 01/96 to 07/05 were included. Salvage surgery was performed either for local recurrence or suspected persistent nodal disease. Complete tumor removal, perioperative morbidity, and overall survival were analyzed in a retrospective study. 28 out of 134 patients underwent salvage surgery after primary treatment with induction chemotherapy and radiotherapy for advanced LHC. 15 patients had laryngectomy (LE) with neck dissection (ND), while 1 patient had lasersurgical partial laryngeal resection with ND for local recurrences. Twelve patients had salvage ND for suspicion of persistent lymph node metastases. 73% of LE patients had major postoperative problems such as pharyngocutaneous fistulas. In 56% of the cases, tumor removal turned out to be microscopically incomplete. Eight out of 12 patients who underwent salvage ND because of suspicious lymph nodes (66%) were free of vital tumor. When metastatic disease was present in the neck (4/12), recurrences occurred in 75% during postoperative follow-up. Only 2 out of 20 patients undergoing surgery for histologically proven recurrence after radiochemotherapy (10%) are actually tumor-free and alive after a mean observation time of 43.9 months. Salvage surgery for local recurrence is associated with high morbidity and poor oncological and functional outcome. ND for suspicious persistent nodal disease after radiochemotherapy can be an over-treatment. In our patients, it was burdened with cervical recurrences and distant metastases in presence of histologically confirmed lymph node metastases. In the light of our results, unfavourable outcome after salvage surgery must be pointed out when initially informing patients about different therapeutic options for advanced LHC.

Surgical salvage of cancer of the oropharynx after chemoradiation

Advanced oropharyngeal squamous cell carcinoma is treated primarily with chemoradiation, with the goal of excellent disease control and preservation of swallowing and articulation functions of the oropharynx. Disease control rates generally are excellent; however, a significant number of patients do not achieve locoregional control of disease. The importance of human papillomavirus expression in predicting successful tumor response, locoregional control, and survival following chemoradiation is increasingly confirmed. Emerging is a clinical profile, viral expression, and genetic expression pattern that can predict success of chemoradiation and indicate which patients are at higher risk for locoregional failure necessitating surgical salvage. Successful surgical salvage depends on restaging at the time of recurrence and the time interval from chemoradiation to recurrence. Although surgical morbidity and mortality remain a challenge in patients undergoing salvage surgery of the oropharynx after radiation failure with or without chemotherapy, they may be mitigated by liberal application of regional and microvascular free flap reconstruction techniques.

Reirradiation after salvage surgery and microvascular free flap reconstruction for recurrent head and neck carcinoma

To evaluate the outcome and complications of reirradiation of recurrent head and neck cancer after salvage surgery and microvascular reconstruction. Retrospective. Twelve patients underwent salvage surgery with microvascular reconstruction for recurrent or second primary head and neck cancer in a previously irradiated field. Median prior radiation therapy dose was 63.0 Gy. Patients then underwent postoperative reirradiation, and received a median total cumulative radiation dose of 115.0 Gy. Three (25%) patients experienced acute complications (<3 months) during reirradiation. Four (33%) patients developed grade 3 or 4 late reirradiation complications (>3 months). There were no incidences of free flap failure, brain necrosis, spinal cord injury, or carotid rupture. The incidence of soft tissue necrosis and osteoradionecrosis was 8%. Six (50%) patients are alive without evidence of recurrent disease a median of 40 months after reirradiation. Microvascular free flaps allow for maximal resection and reliable reconstruction of previously irradiated cancers before high dose reirradiation and may reduce the incidence of severe late complications and treatment related mortality.

Reirradiation After Surgery and Microvascular Reconstruction

Problem To evaluate the outcome and complications of reirradiation of recurrent head and neck cancer after salvage surgery and microvascular reconstruction. Methods Retrospective Study. Twelve patients underwent salvage surgery with microvascular reconstruction for recurrent or new primary head and neck cancer in a previously irradiated field. Median prior RT dose was 63.0 Gy (range 30.0–72.8). Patients then underwent postoperative reirradiation, receiving a median total cumulative radiation dose of 115.0 Gy. Results Three patients (25%) experienced acute complications (&lt;3 months) during reirradiation that resolved with conservative care. Four patients (33%) developed grade 3 or 4 late reirradiation complications (&gt;3 months). There were no incidences of free flap failure. No patients suffered brain necrosis, spinal cord injury, or carotid rupture. The incidence of soft tissue necrosis and osteoradionecrosis was 8%. There were no treatment-related mortalities. Six patients (50%) are alive without evidence of recurrent disease a median of 40 months after reirradiation (range 4–64 months). Conclusion Free flap reconstruction followed by reirradiation is not associated with an increased risk of perioperative, acute, or late complications. Microvascular free flaps allow for maximal resection and reliable reconstruction of previously irradiated cancers before high dose reirradiation, and may reduce the incidence of severe late complications and treatment related mortality. Significance Reirradiation for recurrent head and neck squamous cell carcinoma remains controversial. However, increasing evidence has demonstrated improved survival and locoregional control with reirradiation at the cost of potentially severe or sometimes fatal radiation toxicity. We hypothesize that using well-vascularized tissue and bone at the time of salvage surgery can reduce the incidence of reirradiation complications. This would allow patients at high risk for recurrence to more safely receive a second course of radiation therapy. To our knowledge this is the first report of the effects of microvascular reconstruction on complications and outcomes of patients undergoing salvage surgery and external beam reirradiation.

Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy

The optimal treatment for patients with locally recurrent carcinomas of the salivary glands is unclear. Ninety-nine patients underwent salvage surgery for locally recurrent salivary gland carcinomas. Eighty-one (82%) had previously received radiation. Thirty-seven patients (37%) received intraoperative radiation therapy (IORT) to a median dose of 15 Gy (range, 12-18 Gy) at the time of salvage. The 1-, 3-, and 5-year estimates of local control after salvage surgery were 88%, 75%, and 69%, respectively. A Cox proportional hazard model identified positive margins (0.01) and the omission of IORT (p = .001) as independent predictors of local failure. The 5-year overall survival was 34%. Distant metastasis was the most common site of subsequent failure, occurring in 42% of patients. IORT significantly improves disease control for patients with locally recurrent carcinomas of the salivary glands. The high rate of distant metastasis emphasizes the need for effective systemic therapies.

Mechanisms of sunitinib malate (SU) resistance in gastrointestinal stromal tumors (GISTs)

10006 Background: SU, an oral, multitargeted inhibitor of KIT, PDGFRs, VEGFRs, FLT3, and RET receptor tyrosine kinases, is now the standard therapy for treatment of imatinib mesylate (IM)-resistant GIST tumors or IM-intolerant GIST patients. However, it is unclear if the clinical efficacy of SU in this setting is due to inhibition of KIT and/or PDGFRA in tumor cells, inhibition of VEGFRs and PDGFRs in endothelial cells and pericytes, respectively, or a combination of antitumor and antiangiogenic effects. In order to address this question, we studied the molecular mechanisms of SU resistance in vitro and in patient-derived tumors. Methods: We studied the in-vitro effects of IM or SU on cells with KIT exon 11 mutations, either alone or in combination with known IM-resistant secondary mutations. In addition, we analyzed tumor samples obtained from patients undergoing salvage surgery after SU treatment failure. Tumor specimens were genotyped for primary and secondary mutations. Results: SU was approximately 2–5-fold more potent than IM against typical GIST-associated KIT exon 11 mutations. In addition, the presence of secondary mutations involving the ATP/drug binding pocket (V654A or T670I) did not substantially alter SU potency. In contrast, these ATP/drug-binding-pocket mutations conferred high-level resistance to IM. However, SU had no significant inhibitory effect on the kinase activity of secondary IM-resistant mutations involving the KIT activation loop (exon 17, codons 816, 820, 822, and 823). Surgical resection was performed on two GIST patients who had clinical progression on SU. Among nine progressing lesions, substitutions were detected in codons 816, 820, and 822; a novel mutation, L783V, was also identified. In contrast, two non-progressing tumors both contained a V654A secondary mutation. Conclusions: Consistent with in-vitro studies, acquired IM-resistant mutations of the KIT activation loop in GIST are associated with clinical resistance to SU and IM. In addition, novel kinase mutations not previously associated with IM resistance may contribute to clinical SU resistance. These findings suggest that the antiangiogenic effects of SU may be insufficient to inhibit GIST progression when the targeted oncogenic kinase remains active. [Table: see text]

Salvage Surgery with Free Flap Reconstruction: Factors Affecting Outcome After Treatment of Recurrent Head and Neck Squamous Carcinoma

To determine factors predicting the outcome after salvage surgery with microvascular flap reconstruction for recurrent squamous cell cancer (SCC) of the head and neck. This is a retrospective analysis of patients treated at an academic medical center. One hundred six patients underwent salvage surgery and microvascular flap reconstruction after prior unsuccessful cancer treatment using surgery, radiation, or chemotherapy. All patients had a follow-up interval after salvage surgery of at least 24 months unless cancer rerecurrence occurred within 24 months after salvage surgery. Factors including age, sex, comorbidity level, tobacco use, alcohol use, disease-free interval since prior therapy, prior radiation, prior chemotherapy, prior surgery, recurrent tumor T class, recurrent tumor N class, recurrent cancer stage, and tumor location were examined to determine their association with cancer rerecurrence after salvage surgery. Successful treatment was defined as patients who remained free from cancer rerecurrence for a minimum 2 year period after salvage surgery. Advanced recurrent T class (P = .02) was significantly associated with cancer recurrence. Recurrent cancer stage and patient smoking status approached statistical significance (P = .06). Patients with recurrent T1 and T2 class are the best candidates for salvage surgery and microvascular flap reconstruction for treatment of recurrent SCC of the head and neck. Patients with T3 and T4 class recurrent cancers and patients who continue to smoke after initial diagnosis and treatment of head and neck SCC are poor candidates to undergo salvage surgery.

Salvage Surgery for Recurrent Carcinoma of the Hypopharynx and Reconstruction Using Jejunal Free Tissue Transfer and Pectoralis Major Muscle Pedicled Flap

To evaluate patients undergoing salvage surgery after recurrent squamous cell carcinoma of the hypopharynx. Retrospective analysis. All patients underwent surgery and follow-up evaluations at the Medical University of Vienna. The departments of Surgery and Otorhinolaryngology carried out patient care and analysis of data. A total of 8 consecutive patients with recurrent hypopharyngeal squamous cell carcinoma. An interdisciplinary team of surgeons, including a head and neck surgeon, a reconstructive surgeon, and an abdominal surgeon, performed salvage surgery. After pharyngolaryngectomy and neck dissection, reconstruction using free, autotransplanted jejunum covered by a pectoralis major muscle flap was achieved. All data concerning the surgical procedure, perioperative morbidity, and functional and oncologic outcome were reviewed. The cohort of patients was heavily pretreated owing to late stages of disease at diagnosis. Mean time to recurrence before salvage surgery was 7.5 months. Mean time after surgery until ability to swallow was regained was 17.2 days, including 1 patient who ultimately underwent interventional dilation owing to stenosis. There were no complications requiring further surgical therapy, and all patients were transferred to outpatient care within 2 months. Three patients, all with advanced nodal involvement, died within months after surgery. Five patients are alive, 4 of whom have shown no evidence of disease 4 years or more after salvage surgery. Jejunal transfer and pectoralis major muscle flap were carried out in a single, reconstructive procedure after salvage resection in hypopharyngeal carcinoma. Potential long-term survival and minor perioperative and postoperative morbidity can be achieved using an interdisciplinary approach.