Rethinking the 10-pack-year rule for favorable human papillomavirus-associated oropharynx carcinoma: A multi-institution analysis.

BACKGROUND: De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. METHODS: From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). RESULTS: Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. CONCLUSIONS: The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.

Extent of pathologic extracapsular extension and outcomes in patients with nonoropharyngeal head and neck cancer treated with initial surgical resection.

BACKGROUND: Lymph node extracapsular extension (ECE) is a known adverse prognostic factor in head and neck cancer and is an indication for adjuvant chemoradiation (CRT). However, the extent of ECE may provide additional prognostic information in the setting of adjuvant CRT. METHODS: This study included 350 patients with oral cavity cancer (72.6%) or bulky/nonfunctional laryngeal cancer (27.4%) who underwent initial surgical resection. Extent of ECE was graded from 0 to 4 based on the scale established by Lewis and colleagues. Multivariable analyses (MVA) were adjusted for primary site, pathologic risk factors, and adjuvant therapy. RESULTS: In univariate failure-free survival (FFS) analysis, there was no significant difference in FFS for patients with lymph node-positive disease and no ECE (grade 0) versus patients with ECE grades 1 through 3. However, patients with ECE grade 4 had significantly worse FFS. In MVA for FFS, differences between ECE grades 0 through 3 and grade 4 did not remain significant. In MVA of overall survival, ECE grade 4 was significantly associated with higher risk of death compared with ECE grade 0 (hazard ratio, 0.46; P = .02) and ECE grades 1 through 3 (HR, 0.41; P = .01). CONCLUSIONS: Dichotomous evaluation of ECE is useful for determining appropriate adjuvant therapy but has limited additional prognostic value in the setting of adjuvant CRT. The detrimental effect of ECE grades 1 through 3 relative to no ECE is effectively mitigated with adjuvant CRT, but ECE grade 4 retains a poorer prognosis despite CRT with regard to overall survival. Patients with ECE grade 4 may be candidates for trials investigating novel methods of adjuvant therapy intensification.

Enhanced Recovery After Surgery and Perioperative Laryngectomy Outcomes.

OBJECTIVE: Patients undergoing laryngectomy are particularly vulnerable to postoperative complications secondary to social and nutritional barriers, substance abuse, and prior cancer treatment. Enhanced Recovery After Surgery (ERAS) programs may mitigate this vulnerability and improve postoperative complications and oncologic outcomes. The objective of this study is to evaluate the postoperative complication rate and oncologic outcomes of patients undergoing laryngectomy before and after ERAS program implementation. METHODS: A historic cohort of 50 patients who underwent laryngectomy at the Levine Cancer Institute, Charlotte, North Carolina from 2014 to 2019 (pre-ERAS) was compared to 33 patients who underwent laryngectomy after ERAS implementation from 2019 to 2020. The primary outcomes included length of stay (LOS), Clavien-Dindo postoperative complications through 30 days following discharge, overall survival (OS), and recurrence-free survival between pre-ERAS and ERAS groups. RESULTS: Demographic characteristics between the two groups were similar. ERAS pathway implementation led to core care element consistency and improvement in the clinical perioperative course, including preoperative nutritional intervention (p = 0.009), postoperative ventilator independence (p = 0.0004), and refractory nausea/emesis (p = 0.18). Severe (≥ grade 3) complications (p = 0.49) and LOS (p = 0.68) were similar between groups. No significant difference in Cox proportional modeling of OS (p = 0.60) or recurrence-free survival (p = 0.17) was noted. CONCLUSIONS: ERAS did not improve LOS, major postoperative complications, or oncologic outcomes in this cohort of patients who underwent laryngectomy. However, ERAS positively influenced secondary endpoints within the laryngectomy perioperative course, conferring qualitative health care benefits. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2262-2268, 2024.

Weekly Versus Bolus Cisplatin Concurrent With Definitive Radiation Therapy for Squamous Carcinoma of the Head and Neck: A Systematic Review and Network Meta-Analysis.

PURPOSE: The schedule of cisplatin concurrent with definitive radiation for squamous carcinoma of the head and neck remains controversial. Most institutions deliver either a high-dose "bolus" schedule once every 3 weeks or a low-dose weekly schedule. We compared these 2 schedules via a simplified network meta-analysis with a common comparator. METHODS AND MATERIALS: We performed a PRISMA-concordant systematic review to identify randomized controlled trials comparing cisplatin with cetuximab for nonmetastatic, locoregionally advanced squamous carcinoma of the head and neck treated with definitive radiation. Trials incorporating primary surgery or induction therapy were excluded. Patient survival times were extracted on a per-event basis from the published curves using a digitizer and validated against published point estimates and hazard ratios (HRs). Survival was compared using random effects Cox regression under a frequentist framework. Toxicity and secondary endpoints were analyzed qualitatively. The Cochrane method assessed the risk of bias. The analysis plan was preregistered with the Open Science Foundation. RESULTS: Five randomized trials were identified, including 1678 patients. There was no statistical difference in overall survival between weekly and bolus regimens (HR, 0.90; 95% CI, 0.53-1.52, P = .345). This Cox model suggested that for the average patient in the cohort, the absolute difference in 5-year overall survival between weekly and bolus regimens was +1.2% (95% CI, -6.1%-+5.9%, P = .345). Secondary endpoints and toxicity were not obviously different by regimen, qualitatively. CONCLUSIONS: The cetuximab trials provide indirect data suggesting that the differences between cisplatin schedules are subtle.

Factors associated with oral hygiene compliance in patients treated with radiation therapy for head and neck cancer.

BACKGROUND: Patients who are oral hygiene noncompliant (OHNC) are more likely to lose teeth after radiation therapy (RT) for head and neck cancer (HNC), which increases the risk of developing osteoradionecrosis. A previous study revealed that patients who were OHNC at baseline (BL) who became oral hygiene compliant during follow-up had the best tooth-failure outcomes. The purpose of this study was to identify factors associated with oral hygiene compliance (OHC), overall, and among those who were BL OHNC. METHODS: This was an observational, prospective, cohort study of 518 patients with HNC assessed before RT and at post-RT follow-up visits every 6 months for 2 years. Patient and treatment-related information was collected at BL and during follow-up, including self-reported OHC. OHC was defined as toothbrushing at least twice daily and flossing at least once daily. RESULTS: Of the 296 patients who self-reported being BL OHNC, 44 (14.9%) became oral hygiene compliant at all follow-up visits. Among this group, those who had dental insurance (P = .026), surgery before RT (P = .008), limited mouth opening before RT (P = .001), compliant fluoride use (P = .023), primary RT site of oral cavity (P = .004), and primary surgical site of larynx and hypopharynx (P = .042) were more likely to become oral hygiene compliant post-RT. CONCLUSIONS: The reasons for the cohort of patients with HNC in this study being OHNC are multifaceted and relate to socioeconomic factors and cancer characteristics. PRACTICAL IMPLICATIONS: Finding ways to increase OHC and fluoride use among patients with HNC who are at greatest risk of being OHNC should be explored.

Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways.

We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulation blockade regimen achieved sustained insulin independence (median survival, >140 days) without evidence of porcine endogenous retrovirus dissemination. Thus, neonatal porcine islets represent a promising solution to the crucial supply problem in clinical islet transplantation.

Impact of nutritional compliance within ERAS protocols for hepatopancreatobiliary, radical cystectomy, and head and neck procedures: A case-matched analysis adjusted for major complications.

BACKGROUND: Enhanced recovery after surgery (ERAS®) pathways aim to improve patient outcomes by applying multimodal practices before, during, and after operative procedures. Compared with standard care before ERAS, we investigated whether compliance to ERAS guidelines for nutritional care, preoperative oral carbohydrate loading and postoperative oral nutrition, was associated with a decrease in hospital length of stay (LOS) after pancreaticoduodenectomy, distal pancreatectomy, hepatectomy, radical cystectomy, and head and neck tumor resection with reconstruction. METHODS: Compliance to ERAS nutrition recommendations was evaluated. Post-ERAS cohort was retrospectively analyzed. Pre-ERAS cohort consisted of case matched patients one year before ERAS: age more than or less than 65 years, body mass index (BMI) more than greater than or less than 30 kg/m2, diabetes mellitus, sex, and procedure. Each cohort consisted of 297 patients. Binary linear regressions evaluated the incremental effect of postoperative nutrition timing and preoperative carbohydrate loading on LOS. Multivariate regressions adjusted for postoperative complications. RESULTS: Compliance with preoperative carbohydrate loading for the post-ERAS cohort was 81.7%. Mean hospital LOS was significantly shorter for the post-ERAS cohort compared with pre-ERAS cohort (8.3 vs 10.0 days, p < 0.001). By procedure, LOS was significantly shorter for patients undergoing pancreaticoduodenectomy (p = 0.003), distal pancreatectomy (p = 0.014), and head and neck procedures (p = 0.024). Early postoperative oral nutrition was associated with a 3.75-day shorter LOS (p < 0.001); no nutrition was associated with a 3.29-day longer LOS (p < 0.001). CONCLUSION: Compliance with ERAS protocols for specific nutritional care practices was associated with a statistically significant decrease in LOS without subsequent increases in 30-day readmission rates and positive financial impact. These findings suggest that ERAS guidelines for perioperative nutrition are a strategic pathway to improved patient recovery and value-based care in surgery.

Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era.

OBJECTIVE: Small carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. PATIENTS AND METHODS: A retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. RESULTS: From 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68-70.2 Gy in 33-35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1-28.8%). CONCLUSION: Small tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

Defining targets to improve care delivery for T4 larynx squamous cell carcinoma.

Objective: United States oncology trends consistently demonstrate that nearly half of T4a larynx carcinoma patients are treated with larynx preservation, despite national guidelines favoring laryngectomy. This study identifies clinical decision-making drivers and defines patient subsets that should become targets for care improvement. Methods: Retrospective analysis of patients with cT4 squamous cell carcinoma of the larynx from US National Cancer Database 2005-2016. Demographic data and survival rates between clinical pathways were compared. Survival was estimated by Kaplan-Meier method with statistical comparisons assessed by log-rank test. Results: Of 11,556 patients with cT4 disease, laryngectomy (TL) was the initial treatment for 4627 (40%) patients. Larynx preservation via chemoradiation (CRT) occurred for 4307 patients. TL and CRT patients had similar Charlson-Deyo comorbidity indices and insurance status. TL patients had higher total tumor size, lower N3 rates and were more often seen at academic institutions (p < .0001). N0 surgery patients with adjuvant treatment demonstrated superior median survival (MS) compared to CRT (surgery + radiation MS: 69 months, surgery + chemoradiation MS: 66, CRT MS: 37.7), p < .0001. MS for N1/N2 disease patients was 56.5 months for surgery + radiation and 35.5 months for surgery + CRT, superior to CRT, MS 30.8 months, p < .0001. Tri-modality N3 patients with up front surgery had similar MS compared to CRT (surgery + chemoradiation 21.3 months vs. CRT 16.1), p = .95. Conclusion: National quality improvement initiatives are needed to promote guideline adherence and improve survival in advanced larynx cancer. Targets for such initiatives should be patients with limited or no nodal disease burden, that meet clear T4a imaging criteria. Level of Evidence: Level IV, non-randomized controlled cohort.

Survivorship Care Plans Improve the Identification of Post-radiation Hypothyroidism After Head and Neck Cancer Treatment.

BACKGROUND/AIM: Survivorship care programs (SCPs) educate patients on post-treatment side-effects, which may lead to earlier identification and mitigation of their impact. This study assessed the impact of SCP on identification and management of post-treatment hypothyroidism in a head and neck cancer population and evaluated socio-demographic factors in the effectiveness of SCPs. PATIENTS AND METHODS: A retrospective analysis was performed of sociodemographic and clinical characteristics of patients with head and neck cancer treated with radiation therapy between January 2011 and January 2019 at a large community cancer institution. Development of hypothyroidism was defined as elevated thyroid-stimulating hormone (TSH) or initiation of supplementation post-treatment. Cumulative incidence of hypothyroidism was analyzed with Gray's method. RESULTS: Of 608 patients, 483 (79%) had post-treatment TSH surveillance. A total of 203 (42%) of those patients developed hypothyroidism; 53 (11%) patients completed SCPs. The median follow-up was 1.4 (interquartile range=0.7-2.6) years with a median time until diagnosis of hypothyroidism of 1.2 (interquartile range=0.7-2.1) years. The median time to diagnosis was 12.0 months with SCP versus 14.2 months without. Race and insurance status were not associated with differences in thyroid surveillance. Patients with laryngeal cancer were at greatest risk of developing hypothyroidism (hazard ratio=1.92, confidence interval=1.44-2.56; p<0.077). Cumulative incidence of post-treatment hypothyroidism was higher in patients managed with SCP, 65.4% at 4 years, compared to those without (49.0%). Receipt of SCP was independently associated with an increased incidence of hypothyroidism detection (hazard ratio=1.51, confidence interval=1.04-2.20; p=0.030). CONCLUSION: In our experience, SCP utilization was independently associated with a diagnosis of hypothyroidism. This study supports implementation of a survivorship program for identification and management of post-treatment sequelae.

Anti-CD40 monoclonal antibody synergizes with CTLA4-Ig in promoting long-term graft survival in murine models of transplantation.

Blockade of the CD40/CD154 signaling pathway using anti-CD154 Abs has shown promise in attenuating the alloimmune response and promoting long-term graft survival in murine model systems, although side effects observed in humans have hampered its progression through clinical trials. Appropriately designed anti-CD40 Abs may provide a suitable alternative. We investigated two isoforms of a novel monoclonal rat anti-mouse CD40 Ab (7E1) for characteristics and effects mirroring those of anti-CD154: 7E1-G1 (an IgG1 isotype); and 7E1-G2b (an IgG2b isotype). In vitro proliferation assays to measure the agonist properties of the two anti-CD40 Abs revealed similar responses when plate bound. However, when present as a soluble stimulus, 7E1-G1 but not 7E1-G2b led to proliferation. 7E1-G2b was as effective as anti-CD154 when administered in vivo in concert with CTLA4-Ig in promoting both allogeneic bone marrow chimerism and skin graft survival, whereas 7E1-G1 was not. The protection observed with 7E1-G2b was not due to depletion of CD40-bearing APCs. These data suggest that an appropriately designed anti-CD40 Ab can promote graft survival as well as anti-CD154, making 7E1-G2b an attractive substitute in mouse models of costimulation blockade-based tolerance regimens.

Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design.

OBJECTIVES: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. MATERIALS AND METHODS: From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. RESULTS: We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2-4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). CONCLUSION: Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.

Magnetic resonance imaging features of pilocytic astrocytoma of the brain mimicking high-grade gliomas.

OBJECTIVE: The typical magnetic resonance/computed tomographic imaging appearance of pilocytic astrocytoma (PA) is that of a cyst with an intensely enhancing mural nodule. The purpose of this study was to illustrate the aggressive imaging features of PA. METHODS: One hundred patients referred to the cancer center with brain tumors histologically proven to be PA were retrospectively reviewed (95 by magnetic resonance imaging and 5 by computed tomographic imaging) and analyzed. RESULTS: The patient population includes 76 pediatric patients younger than 18 years and 24 adults ranging from 19 to 45 years old. Tumor locations consisted of the following: optic chiasm (22), lateral ventricle (3), thalamus (12), basal ganglia (1), cerebral hemisphere (10), corpus callosum (2), brain stem (26), fourth ventricle (1), and cerebellum (23). The imaging appearance of PA consisted of typical features in 71 cases and aggressive features in 29 cases. CONCLUSIONS: It is important to recognize the aggressive imaging appearance of PA (grade 1 astrocytoma) because it can be mistaken for high-grade gliomas and may thus lead to inappropriate therapy. Despite the aggressive imaging appearance of PA, there is no histopathologic evidence of anaplasia.

Cutaneous manifestations associated with malignancy of the head and neck.

Most cutaneous malignancies of the head and neck (HN) are non-melanoma skin cancers, predominantly basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Less common entities include Merkel cell carcinoma (MCC), sebaceous carcinoma (SC), and angiosarcoma. Treatment is based on histology subtype, stage, and extent of involvement. Surgery is the primary means of treatment and includes wide local excision, Mohs micrographic surgery, sentinel lymph node biopsy, and cervical lymphadenectomy. Multidisciplinary management including radiation and targeted chemotherapy are critical adjuncts to surgery. Surgical planning must balance oncologic, functional, and cosmetic considerations. This review addresses cutaneous manifestations of primary malignancies of the HN and dermatologic complications of small molecule inhibitors used for targeted therapy. A working knowledge of both the cutaneous malignancies (CM) in the head and neck as well as the secondary dermatologic manifestations is relevant to multiple disciplines including dermatology, medical oncology, radiation oncology, and surgical oncology.

Well-differentiated thyroid cancer with aerodigestive tract invasion: Long-term control and functional outcomes.

BACKGROUND: Well-differentiated thyroid cancer (WDTC) invading the aerodigestive tract is an uncommon entity associated with significant morbidity and reduced survival. METHODS: We reviewed the surgical treatment, oncologic control, and functional outcomes of 69 consecutive patients with WDTC invading the upper aerodigestive tract. RESULTS: Complete tumor excision with negative margins was achieved in 62% of patients. Tracheostomy dependence (27%) and permanent hypoparathyroidism (49%) were present or the result of surgery. Seventy-one percent of patients ate a regular diet, 59% had normal speech, and the majority (62%) reported normal activities of daily living. The local, regional, and distant recurrence was 1%, 14%, and 23%, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) was 71% and 45%, respectively. CONCLUSION: Surgical resection and appropriate adjuvant treatment can achieve excellent locoregional control while preserving function and quality of life. Long-term survival is limited by the high incidence of distant metastasis.

Pediatric blunt trauma resulting in major arterial injuries.

Ten children, aged 4 to 14 years, sustaining blunt arterial trauma from motor vehicle collisions (6), bicycle accidents (2), and falls (2) were identified over a 10-year period. The arteries injured included the common iliac (3), abdominal aorta (2), carotid (2), brachial (2), and the subclavian, renal, and femoral artery (1 each). One patient had three arterial injuries. Six patients had associated injuries including a pelvic and lumbar spine fracture, Horner's syndrome, liver laceration, skull fracture, open humerus fracture, small bowel serosal tear, and a brachial plexus injury. Definitive diagnosis was made using arteriography (6), computed tomography (CT) scan (2), and physical examination (2). The types of arterial injuries found included incomplete transection, complete transection with pseudo-aneurysm formation, traumatic arteriovenous (AV) fistulas, complete occlusion, and dissection. Repair was accomplished by hypogastric artery interposition or bypass grafting, synthetic grafting with polytetrafluoroethylene (PTFE), reverse saphenous vein grafting, or primary repair, depending on the circumstances. An AV fistula between the carotid artery and cavernous sinus was embolized. All grafts remained patent with exception of the aorto-renal bypass graft at follow-up ranging from 1 month to 3 years. The principles for repairing vascular injuries in children are slightly different than those in adults. Every effort should be made to use autogenous tissue such as the hypogastric artery or saphenous vein for repair if possible. If not, PTFE grafts can be used, although the long-term patency of these grafts in growing children is not known.

The role of parotidectomy in Sjögren's syndrome.

Sjögren's syndrome, a chronic and progressive autoimmune disorder mainly characterized by xerophthalmia, xerostomia, and parotid enlargement, is primarily managed medically, but some patients will require surgical management. Patients with Sjögren's syndrome have an increased risk of non-Hodgkin lymphoma. Superficial parotidectomy is indicated for diagnostic purposes and can be therapeutic in limited circumstances. Surgical indications for parotidectomy in Sjögren's syndrome include recurrent parotitis refractory to medical management; salivary gland malignancy; and severe, refractory pain. Surgical complications include transient or permanent facial nerve injury, post-operative pain, persistent inflammation of remnant parotid tissue, Frey syndrome, and facial scarring.

Poly (ADP-ribose) polymerase inhibitors in cancer treatment.

Recent research on inhibitors of poly (ADP-ribose) polymerase (PARP) has demonstrated their potential for improving cancer therapy. They inhibit protein poly (ADP-ribosyl)ation and thus affect numerous molecular and cellular functions, including DNA repair and cell survival, that are critical for such physiological and patho-physiological states as carcinogenesis, inflammation, and resistance to cancer therapy. In this review, we describe the biological basis underlying the use of these agents in cancer therapy, providing data from preclinical studies that demonstrate the synergistic interaction of PARP inhibitors with radiation and chemotherapeutics. We also summarize initial clinical trials of PARP inhibitors for cancer treatment.