Stereotactic body radiation therapy (SBRT) of adrenal gland metastases in oligometastatic and oligoprogressive disease.

BACKGROUND: Stereotactic body radiation therapy (SBRT) as a form of noninvasive treatment that is becoming increasingly used to manage cancers with adrenal gland metastases. There is a paucity of data on safety and efficacy of this modality. The aim of the study was to evaluate the safety and efficacy of adrenal gland SBRT in oligometastatic and oligoprogressive disease. MATERIALS AND METHODS: In this retrospective study, we performed a single-institution analysis of 26 adrenal lesions from 23 patients with oligometastatic or oligoprogressive disease treated from 2013 to 2019 with the goal of achieving durable local control. Palliative cases were excluded. Radiation dosimetry data was collected. Kaplan Meier product estimator and Cox proportional hazards regression analysis were used for statistical analysis. RESULTS: The median dose was 36 Gy in 3 fractions (range: 24-50 Gy and 3-6 fractions) with a median biologically effective dose (BED10) of 72 (range: 40-100). 1-year local control rate was 80% and median local control was not achieved due to a low number of failures. 1- and 2-year overall survival rates were 66% and 32%. Toxicity was mild with only one case of grade 2 nausea and no grade 3-5 toxicity. Higher neutrophil to lymphocyte ratio was associated with worse overall survival and a trend toward worse progression-free survival. In addition, worse performance status and lower BED10 were associated with worse survival. No such association could be shown for primary tumor location, histology, size or stage. CONCLUSION: Adrenal SBRT for oligometastatic or oligoprogressive disease is a safe and effective form of treatment.

Surface mould brachytherapy in oral and oropharyngeal cancers.

INTRODUCTION: There are insufficient data on surface mold brachytherapy (SMB) in treating oral cancers. We reviewed our institutional experience to investigate the efficacy and toxicity of this treatment modality. MATERIAL AND METHODS: We retrospectively reviewed all the patients treated between 1989 and 2018 with high-dose-rate iridium-192 SMB for oral and oropharyngeal squamous cell carcinomas at our institution. Surface mold brachytherapy was delivered via an acrylic surface mold with 1-5 inserted catheters spaced 1 cm apart fabricated by our dental oncologist. The Kaplan-Meier product estimator was used to assess local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Cox proportional hazards regression analysis was used to assess the relationship of various variables and patient outcomes. RESULTS: Eighteen patients met the inclusion criteria and were evaluated. Indications for treatment were primary tumor (n = 13), local recurrence (2), locoregional recurrence (1), and oligometastatic disease (1). Ten patients received SMB alone and 8 received external beam radiotherapy with an SMB boost. The acute toxicity outcomes were as follows: no toxicity (n = 1), grade 1 (7), grade 2 (9), and grade 3 (1). Late effects were rare, only occurring in 3 patients. The one- and two-year LC were 81% and 68%, LRC 77% and 64%, DMFS 81% and 81%, and OS 77% and 46%. CONCLUSIONS: Surface mold brachytherapy is a viable modality as either primary or boost treatment for superficial oral cancers. In our patients, this treatment method has a low toxicity profile and resulted in reasonable LC.

Prognostic factors and selection criteria in the retreatment of head and neck cancers.

OBJECTIVES: To determine predictors of treatment selection, outcome, and survival, we examined a cohort of previously irradiated head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: We retrospectively analyzed 100 patients at our institution who were treated for recurrent or second primary (RSP) HNSCC, focusing on subgroups receiving reirradiation (ReRT) alone and those undergoing surgical salvage (SS) with or without post-operative reirradiation therapy (POReRT). Logistic regression modeling was performed to identify factors predictive of retreatment modality. Cox regression modeling was used to determine prognostic factors for progression free survival (PFS) and overall survival (OS). RESULTS: ReRT alone was less likely in current smokers and neck recurrences, with reirradiation more likely in primary site recurrences. POReRT was significantly more likely in patients with positive surgical margins (PSM), neck dissection, or organ dysfunction. POReRT omission negatively impacted PFS when PSM (HR: 8.894, 95% CI: 1.742-45.403) and perineural invasion (PNI) (HR: 3.391, 95% CI: 1.140-10.089) were present. Tracheostomy was associated with worse OS, but ReRT alone and POReRT improved OS. PSM correlated with worse OS, regardless of whether POReRT was given (HR: 14.260, 95% CI: 2.064-98.547). CONCLUSION: This analysis confirms known factors for predicting outcome and shows nonsmoking status and primary site recurrence as predictors for ReRT alone. POReRT for PSM and PNI improves PFS. Tracheostomy patients are more likely to have ReRT due to acute toxicity not limiting treatment and POReRT improves OS compared to surgery alone. The presence of PSM negatively impacts survival which cannot be overcome by POReRT.

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.

PURPOSE: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. METHODS AND MATERIALS: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. RESULTS: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. CONCLUSIONS: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.

Prognostic significance of HPV status in postoperative squamous-cell carcinoma of the head and neck.

BACKGROUND: There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting. OBJECTIVE: To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting. METHODS: We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators. RESULTS: Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; 𝑃 = .010 and 𝑃 = .018, respectively). LIMITATIONS: Retrospective, single-institution study; small patient cohort; short follow-up time. CONCLUSION: The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.

Human papillomavirus E7 serology and association with p16 immunohistochemistry in squamous cell carcinoma of the head and neck.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with improved survival and treatment response as compared to HPV-negative cancers. P16 overexpression is widely accepted as a surrogate marker for HPV positivity. METHODS: A total of 92 serum samples from 75 head and neck squamous cell carcinoma (HNSCC) patients were examined for HPV16 and 18 E7 antibodies by ELISA. Available tissue was tested for HPV-DNA by PCR, and p16 immunohistochemistry was obtained from a deidentified database. RESULTS: Of 75 HNSCC patients, 25 were HPV E7 seropositive. Seropositivity was strongly associated with cancers of the oropharynx, and correlated with positive p16 immunohistochemistry (IHC) and HPV-DNA. Post-treatment serum was available in a limited subset of patients, revealing a decrease in antibody titers following response to treatment. CONCLUSIONS: HPV E7 seropositivity correlated with positive tumor HPV-DNA and p16 expression, and was strongly associated with cancers of the oropharynx. E7 serology warrants further study as a potential biomarker in HPV-positive HNSCC.

Institutional clinical trial accrual volume and survival of patients with head and neck cancer.

PURPOSE: National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown. PATIENTS AND METHODS: The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models. RESULTS: Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment. CONCLUSION: OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC.

Impact of transcutaneous neuromuscular electrical stimulation on dysphagia in patients with head and neck cancer treated with definitive chemoradiation.

BACKGROUND: The purpose of this study was to investigate the role of transcutaneous neuromuscular electrical stimulation (TNMES) therapy in maintaining swallowing function during chemoradiation for locally advanced head and neck cancer. METHODS: We retrospectively compared 43 consecutive patients with locally advanced head and neck cancer treated with TNMES (treatment group) to 55 control patients. Validated swallowing scale scores were assigned. RESULTS: All patients' swallowing scores declined post-chemoradiotherapy. A difference in mean decline in scores for the control group versus the treatment group using the Functional Oral Intake Scale (FOIS) was seen, favoring TNMES intervention (23% vs 7%; p = .015). Age, race, >10 pack-years smoking, diabetes, stage, nodal disease, accelerated fractionation, weight loss, dietary modification, no TNMES, and radiotherapy dose were all significant for poorer scores on the swallowing scales. CONCLUSION: TNMES should be considered an adjunct to dysphagia reduction and possible prevention in patients with locally advanced head and neck cancer. Further studies should be conducted to define the benefit of TNMES intervention.

Evaluation of scrotal and testicular radiation doses for heterotopic ossification prophylaxis.

The majority of patients with heterotopic ossification are males with traumatic injuries in the hip/femur region. The testes, given their proximity, are exposed to scatter radiation, which has the potential to alter sperm count and morphology. In a prospective study, patients were treated with an 800-cGy dose of radiation without direct exposure of the testes/scrotum but with a testicular shield. Thermoluminescent dosimeters were placed inside and outside the shield. Mean dose inside and outside the shield was 10.2 and 20.2 cGy, respectively (sperm abnormalities have been reported with 15 cGy). Given our study results, young males should be counseled and should be treated with a testicular shield.

BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide.

Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.

The relationship of radiation pneumonitis to treated lung volume in breast conservation therapy.

Breast conservation therapy has become a common modality for therapy of early stage breast cancer. Most studies of primary lung irradiation correlate the risk of pneumonitis with the volume of lung treated. It is proposed that the lung volume treated during tangential radiation of the intact breast may be calculated from a measurement of the central lung distance. Central lung distance is the distance from the chest wall to the edge of the field at the central axis. This study examines whether the incidence of radiation pneumonitis indeed correlates with the lung volume treated as calculated from a measurement of the central lung distance. From January 1, 1985, through December 31, 1998, 353 patients were treated with breast conservation therapy at the University of Louisville. The charts were reviewed for any evidence of clinically significant radiation pneumonitis. The treatment films were obtained and the central lung distance ascertained. Four cases of radiation pneumonitis were identified. Three of these occurred after tangential radiation and one occurred in a retreatment field after bone marrow transplant. The overall rate of radiation pneumonitis was 1.2%. A central lung distance of less than 3 cm was found in 78.3% of patients and 21.7% had a central lung distance of three or greater. There was no correlation between central lung distance and the risk of radiation pneumonitis. Breast conservation therapy is a well-tolerated modality for treatment of early stage breast cancer. The incidence of radiation pneumonitis is very low and is usually associated with other factors in addition to the tangential field lung volume.

Hodgkin's lymphoma in adults--clinical features.

One hundred (100) patients were treated in the Department of Radiation Oncology, James Graham Brown Cancer Center, University of Louisville School of Medicine, from 1980-1994. All patients were evaluated and staged according to the accepted guidelines at the treatment times. All patients were followed on a strict follow-up schedule for the outcome of treatment including late effects. The age range was 18 years-77 years. The age groupings are described in Table 1. Eighty-one percent (81%) of the patients were 40 years of age or younger. Nineteen percent (19%) of the patients were older and this was similar to the reported bimodal pattern in Hodgkin's disease. Fifty-eight percent (58%) of the patients were female and the rest were male. Eighty-eight percent (88%) of the patients were Caucasian as depicted in Table 2. Majority of the patients (64) presented with mass in the neck. Some of the patients presented with one or more symptoms and signs. The details of the presentation features are shown in Table 3. Thirty-one percent (31%) of the patients presented with one or more of the 'B' symptoms as described by Cotswolds Staging Classification for Hodgkin's Disease. These include fever (temperature >38 degrees C), drenching night sweats, and unexplained loss of >10% body weight within the preceding 6 months. Appropriate staging included complete physical examination, blood studies, and imaging studies such as plain chest x-rays, lymphangiograms, CT scans, gallium scans, etc. Forty-eight percent (48%) of the patients had staging laparotomy with lymph node sampling, splenectomy, and liver biopsies. The staging was done according to Ann Arbor Staging Classification. Forty-four percent (44%) of the patients were in Stage IIA group and the rest are shown in Table 4. Of the sites of involvement, neck (82 patients) and mediastinum (79 patients) were the common sites. Other sites of involvement are described in Table 5. Many patients had more than one site of involvement. Thirty-three percent (33%) of the patients had bulky mediastinal disease. This was defined based on the ratio of the width of the lesion to the transverse diameter of the chest. The most common histological subtype was nodular sclerosing (73%). This would explain the gender variation in this group of patients. The histological classification was done according to the Rye Classification (Table 6).

Pediatric Hodgkin's disease.

Thirty-two patients were treated in this Department from 1981-1992. The median age was 14 years (range 4 years to 17 years). There are 6 patients (19%) below the age of 10 years, 16 patients (50%) between 11 years to 15 years, and 10 patients (31%) above 16 years. Twenty-three patients (72%) are male and 9 patients (28%) are female. Thirty-one patients (97%) are white, and 1 patient (3%) is Afro-American. The stages of the patients are: Stage I--7 patients, Stage II--12 patients, Stage III--9 patients, and Stage IV--4 patients. Twenty-one patients (66%) in the early period of the study were staged surgically by staging laparotomy. The most common sites are: neck (84%), mediastinum (66%), and para-aortic lymph nodes (22%). Twenty-five patients (78%) have nodular sclerosing type, 5 patients (16%) have mixed cellularity, and 2 patients (6%) have lymphocytic predominant type. Eight patients (25%) were treated with radiation alone and 24 patients (75%) were treated with a combination of chemotherapy and radiation. Of the radiation group, 5 patients were treated with mantle field; 2 patients with mantle, para-aortic node and splenic pedicles; and 1 patient with mini-mantle field. The treatment was given with 4 or 6 mv photon, and the median dose was 36 Gray (range 32-40 Gy). Of the combination group, 11 patients were treated with ABVD (doxorubicin + bleomycin + vinbastine + dacarbazine), 10 patients with ABVD/MOPP (MOPP: mechlorethamine + vincristine + procarbazine + prednisone) and 3 patients with MOPP alone. The median irradiation dose in the combination group was 25 Gy (range 21 Gy-36 Gy). All the patients in this group were treated to the involved site with custom blocks. Three patients were lost for follow-up because of transfers out-of-state and could not be located. All patients in Stages I and II are alive without any evidence of disease at the last follow-up. One patient with Stage III disease developed a second cancer (PNET: primitive neuroectodermal tumor) 111 months after combination treatment and has died. One Stage IV patient has died with Hodgkin's disease 28 months after treatment with combination therapy. All other patients are followed closely along with the primary physicians and consultants.