Phillip M. Devlin

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects

BackgroundThe purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.MethodsUnstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history.ResultsCounts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively.ConclusionHigh salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC.

Gemcitabine-induced radiation recall

PURPOSE To study and report 6 patients with radiation recall in unique sites, secondary to gemcitabine chemotherapy. METHODS AND MATERIALS The clinical presentations and outcomes of 6 patients with radiation recall secondary to gemcitabine chemotherapy were retrospectively analyzed over the course of a 1-year period. RESULTS Radiation recall reactions were seen in the central nervous system, skin, gastrointestinal tract, and in the lymphatic and musculoskeletal systems. The time between initiation of radiation and recall of the radiation phenomenon ranged from 3 weeks to 8 months from the time gemcitabine was initiated. The usual dosage of gemcitabine in these cases was 1000 mg/m(2) given on a weekly basis. No radiation therapy was given concomitantly with gemcitabine. Treatment of the recall reaction consisted of discontinuing gemcitabine and initiating steroid therapy, supportive therapy, and/or nonsteroidal anti-inflammatory agents. Minimal improvement was seen in 3 out of 6 patients, and resolution of the radiation recall was seen in 3 out of 6 patients. A comprehensive review of the literature revealed that radiation recall with gemcitabine has been related to skin reactions only; no previous cases of radiation recall occurring in the central nervous system have been reported with any chemotherapy agent. CONCLUSION Radiation recall from gemcitabine chemotherapy is rare, but can potentially arise in any site that has been previously irradiated. Treating physicians must be aware of this potential toxicity from gemcitabine and radiation and discontinue the gemcitabine if radiation recall is observed.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

PURPOSE To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). METHODS AND MATERIALS TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). RESULTS A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. CONCLUSIONS In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.

Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields

PurposeTo assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSite™ applicator and compare to those produced by whole breast external beam radiotherapy (WBRT).Materials and methodsDosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400 cGy was 1 cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10 Gy or more (V10) and the dose received by 20 cc of the structure (D20), were calculated as well as the maximum and mean doses received.ResultsFifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925–1380 cc. Cardiac volumes ranged from 337–551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction.ConclusionThis study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets.Trial registrationDana Farber Trial Registry number 03-179

American Brachytherapy Society (ABS) consensus statement for sarcoma brachytherapy.

PURPOSE To present recommendations for the use of brachytherapy (BT) in patients with soft tissue sarcoma (STS). METHODS A group of practitioners with expertise and experience in sarcoma BT formulated recommendations for BT in STS based on clinical experience and literature review. RESULTS The indications for adjuvant BT are discussed. There is no consensus on the use of BT alone or in combination with external beam radiation therapy (EBRT), but factors that influence the selection of this modality include tumor grade and size, prior surgeries, and tumor recurrence. Low-dose-rate, high-dose-rate, and pulsed-dose-rate radiation are all acceptable BT modalities to use for STS. Recommendations are made for patient selection, techniques, dose rates, and dosages. Outcome data and toxicity data are reviewed. CONCLUSIONS BT is a useful component of the treatment of STS. The advantages of BT are the targeted dose distribution, low integral dose, and short treatment times. Ultimately the clinician should select the modality or combination of modalities that are most familiar to the treatment team and suitable to the patient.

Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base

The purpose of this study was to examine the long‐term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy.

PERMANENT IODINE-125 INTERSTITIAL PLANAR SEED BRACHYTHERAPY FOR CLOSE OR POSITIVE MARGINS FOR THORACIC MALIGNANCIES

PURPOSE To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy. METHODS AND MATERIALS An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded. RESULTS Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year Kaplan-Meier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year. CONCLUSIONS This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation.

High-dose-rate brachytherapy for prostate cancer in a previously radiated patient with polyethylene glycol hydrogel spacing to reduce rectal dose: Case report and review of the literature

PURPOSE To describe the use of a temporary spacer to reduce rectal dose prior to prostate radiation in a man with prior pelvic radiotherapy and review the relevant literature. METHODS AND MATERIALS A healthy 57-year-old man presented with high-risk prostate cancer (Gleason score of 8, prostate-specific antigen level [PSA] 12.6 ng/mL, T3a by magnetic resonance imaging [MRI]), only 2.5 years after a low anterior resection followed by pelvic chemo-radiotherapy to 50.4 Gy for a locally advanced rectal cancer. Due to the prior radiation, he was not felt to be a candidate for surgery or external beam radiation, so he chose long-term androgen deprivation therapy (ADT) plus high-dose-rate brachytherapy to 36 Gy in 6 fractions. To reduce the radiation dose to the anterior rectal wall, 10 mL of a polyethylene glycol hydrogel spacer was injected between the prostate and rectum and created between 1.4 and 1.5 cm of separation along the length of the prostate. RESULTS Two randomized trials demonstrating that local therapy plus ADT improves overall survival compared to ADT alone provided the rationale for additional prostate radiotherapy in this otherwise healthy patient. Salvage brachytherapy is associated with a 3.4% rate of rectal fistula among the 251 cases reported in the literature from 2000-2007, with rates as high as 12% in one series. The spacer allowed the rectal dose constraint goals to be easily met. CONCLUSIONS Injecting an absorbable polyethylene glycol hydrogel to separate the prostate and rectum appears to be associated with decreased maximum and mean rectal doses, and may have particular utility in previously irradiated patients.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results.

BACKGROUND Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after attempted placement of 10cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS Spacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node-positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.

Partial breast irradiation: a review of techniques and indications

The addition of whole-breast external beam radiotherapy (EBRT) to breast-conserving surgery results in a significant reduction in the risk of death due to breast cancer, but this may be offset by an increase in deaths from other causes and toxicity to surrounding organs. Because of this, and with a view to patterns of local recurrence, irradiation of the tumour bed has been explored in selected patients with early breast cancer using a variety of radiotherapeutic modalities. This review article explores the treatment options for partial breast irradiation and examines their role within the field of breast cancer treatment.