Efficient termination of cardiac arrhythmias using optogenetic resonant feedback pacing.

Malignant cardiac tachyarrhythmias are associated with complex spatiotemporal excitation of the heart. The termination of these life-threatening arrhythmias requires high-energy electrical shocks that have significant side effects, including tissue damage, excruciating pain, and worsening prognosis. This significant medical need has motivated the search for alternative approaches that mitigate the side effects, based on a comprehensive understanding of the nonlinear dynamics of the heart. Cardiac optogenetics enables the manipulation of cellular function using light, enhancing our understanding of nonlinear cardiac function and control. Here, we investigate the efficacy of optically resonant feedback pacing (ORFP) to terminate ventricular tachyarrhythmias using numerical simulations and experiments in transgenic Langendorff-perfused mouse hearts. We show that ORFP outperforms the termination efficacy of the optical single-pulse (OSP) approach. When using ORFP, the total energy required for arrhythmia termination, i.e., the energy summed over all pulses in the sequence, is 1 mJ. With a success rate of 50%, the energy per pulse is 40 times lower than with OSP with a pulse duration of 10 ms. We demonstrate that even at light intensities below the excitation threshold, ORFP enables the termination of arrhythmias by spatiotemporal modulation of excitability inducing spiral wave drift.

FTIR spectroscopy as a convenient tool for detection and identification of airborne Cr(VI) compounds arising from arc welding fumes.

Given the significant presence of the carcinogenic Cr(VI) in arc welding fumes from stainless steels, it is also important, in addition to estimating the Cr(VI) levels, to identify Cr(VI) compounds, as it throws light on the mechanistic pathways towards fume formation. FTIR data is presented in this paper for arc welding fumes collected from Manual Metal Arc Welding (MMA), Flux Cored Arc Welding (FCAW) and Solid Wire Welding (Metal Inert/ Active Gas Welding [MIG/ MAG]). For MMA and FCAW samples, clear spectra corresponding to Na, K, dichromates was observed at wave number of around 725-740 cm-1 and at 890-900 cm-1. Chromate species were also observed at around 850-855 cm-1, as was evidence of CrO3 (chromium trioxide) too (950-970 cm-1). The identification of these compounds was done by carefully identifying the Cr-O-Cr anti-symmetric vibrations, the symmetric stretching of the CrO4 tetrahedra, and the stretching vibrations of the planar CrO3 structure for the chromium trioxide. All the above compounds were volatile, and present as nanoparticles in welding fumes, thereby potentially causing significant harm to the welders. Additionally, crystalline phases (Fe-Mn spinels) were also observed through powder XRD, and the data was compared with ion chromatography estimates for Cr(VI) and found to be consistent.

Reduction of vibration and noise pollution from agricultural tractor engine using novel pine oil and soapnut oil methyl ester as fuel.

The exhaust emissions from automotive diesel engines are successfully controlled over the years by adopting different combustion strategies and after treatment devices, whereas the combustion induced vibration and noise are the major pollutant in off-road vehicle engines and yet to be optimized. In the present study, a twin cylinder, Simpson's S-217 tractor diesel engine was used to evaluate the performance, combustion, vibration, and noise characteristics, using biofuel blends. For this study, the blends of pine oil - soapnut oil biodiesel (P75SNB25), diesel - soapnut oil biodiesel (SNB20) and diesel were used as fuel. The pine oil used in this research was purchased and used in its neat form. The soapnut oil was extracted from the soapnut seeds by cold pressing method and trans-esterified in two stages by using methanol and catalysts. The experimental results revealed that the performance and combustion characteristics of the blend P75SNB25 was superior to diesel and the blend SNB20 was slightly inferior to diesel. For the blend P75SNB25, the amplitude of acceleration with respect to time was reduced by 19.48% and 11.58% at no load and full load conditions respectively, whereas for the blend SNB20, the amplitude of acceleration showed a reduction of 14.27% and 9.46% at no load and full load conditions respectively in comparison with diesel operation. But both the blends P75SNB25 and SNB20 showed a maximum reduction of noise by 2.34% at different engine loads compared to diesel operation.

Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay.

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting. Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients. Results: The average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site. Conclusions: At our tertiary care cancer centre, a patient's clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system.

The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy.

BACKGROUND: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. METHODS: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. RESULTS: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTC(neg) disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTC(pos); P=0.113) and extracapsular extension (CTC(neg); P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). CONCLUSIONS: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.

A Phase 1/2 Trial of Brief Androgen Suppression and Stereotactic Radiation Therapy (FASTR) for High-Risk Prostate Cancer.

PURPOSE: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. METHODS AND MATERIALS: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15 patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. RESULTS: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment. One man was not treated owing to discovery of a synchronous primary rectal cancer. Four patients (26%) experienced grade ≥2 toxicity at 6 weeks after treatment. There were 9 of 15 (60%) who experienced grade ≥2 GI or GU toxicity and 4 of 15 (26%) grade ≥3 GI or GU toxicity at 6 months, and 5 of 15 (30%) grade ≥2 GI and GU toxicity at 6 months. A review of the 15 cases did not identify any remedial changes, thus the phase 1 criteria were not met. CONCLUSION: This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual. Treatment factors, such as inclusion of pelvic lymph node radiation therapy, planning constraints, and treatment margins, or patient factors related to the specific frail elderly population may be contributing.

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population.

BACKGROUND: Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. METHODS: Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. RESULTS: Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. INTERPRETATION: The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.

Adenocarcinoma not otherwise specified on dorsum of tongue: case report and literature review.

Primary adenocarcinoma of the oropharynx most often arises from the minor salivary glands, and primary squamous cell carcinoma is more commonly seen arising from the tongue. Few cases of adenocarcinoma not otherwise specified of the tongue have been reported in the literature, and none found on the dorsum of the tongue. Successful treatment strategies have therefore not been defined.We report a case of adenocarcinoma located on the dorsum of the posterior one third of the tongue adjacent to the circumvallate papillae in a woman presenting with globus sensation and mild dysphagia. Treatment consisted of transoral laser excision and postoperative external-beam radiotherapy, resulting in disease-free survival at her 5-year follow-up. The goals of this report are to present a case of adenocarcinoma arising from the minor salivary gland located on the dorsum of the tongue, to discuss previous reports of similar cases, and to suggest that surgery with or without radiotherapy be used as the mainstay of treatment.

Radiotherapy for steroid-resistant laryngeal Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare lymphoproliferative disorder that can have nodal and extranodal manifestations. In the absence of established guidelines for the management of this condition, various therapeutic modalities are used, including radiotherapy. Radiation dosages and fractionation schedules have not been reported in all instances. We present a case in which glottic and subglottic Rosai-Dorfman lesions causing airway obstruction in a frail steroid-refractory patient were put into complete remission using radiotherapy. The lesions responded transiently to a course of prednisone, but responded completely to external-beam radiation, with minimal side effects to the patient.

Enhanced neogenic potential of Panc-1 cells supplemented with human umbilical cord blood serum--An alternative to FCS.

The promise(s) of using Fetal Calf Serum (FCS) as a supplement for the maintenance of cell cultures has been well documented. However, FCS forms the xenogenic source for any human derived cells/organ and limits its application. Recently, the usage of human umbilical cord blood serum (hUCBS) for maintenance of mesenchymal cells has been supportive. In the present study we investigated the effects of hUCBS and FCS on the proliferation (viability, proliferative) and its differentiation potential (DTZ staining, immunofluroscence) to generate islet like cellular aggregates (ICAs) using the human derived Panc-1 cell lines. A comparative analysis of hUCBS and FCS for each parameter demonstrated that hUCBS supplemented media was better for proliferation and differentiation of the Panc-1 cells. The ICAs obtained from hUCBS primed cultures showed a higher yield, increased islet size, and showed an increase for insulin staining compared to FCS. We suggest that hUCBS can be explored as an alternate serum supplement for FCS, making it more feasible in cell systems of human derived origin and can also find its application for the human transplantation programmes.

Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer.

The objective was to evaluate the relative efficacy of cryoablation (CRYO) versus external beam radiation (EBRT) for clinically locally advanced prostate cancer in a randomized clinical trial. Patients with histologically proven, clinically staged as T2C, T3A or T3B disease were randomized with 6 months of perioperative hormone therapy to one of the two procedures. Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease, only 64 out of the planned 150 patients were accrued. Twenty-one of 33 (64%) in the CRYO group and 14 of 31 (45%) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the CRYO group. The 4-year bDFS for EBRT and CRYO groups were 47 and 13%, respectively. Disease-specific survival (DSS) and overall survival (OS) for both groups were very similar. Serious complications were uncommon in either group. EBRT patients exhibited gastrointestinal (GI) adverse effects more frequently. Taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of CRYO were less favorable compared to those of EBRT, and was suboptimal primary therapy in locally advanced prostate cancer.

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02.

PURPOSE: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. PATIENTS AND METHODS: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. RESULTS: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. CONCLUSION: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

Vocal function following radiation for non-laryngeal versus laryngeal tumors of the head and neck.

OBJECTIVE: The larynx may receive high doses of radiation even in the absence of disease. Preliminary investigation has provided evidence that significant voice alterations exist in patients who received radiotherapy (RT) for non-laryngeal tumors of the head and neck. This study evaluates subjective and objective parameters of vocal function in this patient population compared with a control group of patients irradiated for early glottic tumors. STUDY DESIGN: Retrospective cohort study. METHODS: Vocal function in patients irradiated for non-laryngeal and early glottic tumors was assessed in a comprehensive manner and compared. Microanalytical and macroanalytical acoustic analyses, aerodynamic measurements, and videostroboscopy were performed on vowel production data. The Voice Handicap Index was administered for self-assessment of voice quality. All subjects were male, smokers, and greater than 12 months post-RT. RESULTS: Seventeen patients with non-laryngeal tumors and 13 patients with early glottic tumors were evaluated. Microanalytical acoustic parameters were worse for 75% (6 of 8) of the acoustic measures of vowel production in the non-laryngeal group. These include jitter, relative amplitude perturbation, amplitude perturbation quotient, normalized noise energy, pitch amplitude, and spectral flatness ratio. Macroanalytical acoustic analyses revealed no difference in fundamental frequency but numerically smaller phonational frequency range in the non-laryngeal group. All aerodynamic measures, including mean phonation time, mean airflow, and vocal fold diadochokinetic rate, were decreased in the non-laryngeal group. Videostroboscopy demonstrated increased supraglottic activity in the non-laryngeal group. Voice handicap was significantly greater in the non-laryngeal group. CONCLUSIONS: When compared with patients receiving RT for early glottic tumors, there is objective and subjective evidence of vocal dysfunction in patients treated with wide-field RT for non-laryngeal tumors.

Effects of head and neck radiation therapy on vocal function.

OBJECTIVE: Radiotherapy (RT) is used to treat a variety of head and neck malignancies. The larynx may receive high radiation doses even in the absence of disease. The effects of RT on the nondiseased larynx are unknown. This study will evaluate subjective and objective parameters of vocal function in patients treated with RT for nonlaryngeal malignancies. DESIGN: Cross-sectional observational study. METHODS: Videostroboscopic, aerodynamic, and acoustic analyses were performed. Results were compared to age- and gender-matched controls. Self-assessment of voice quality was measured using the Voice Handicap Index. RESULTS: A majority of patients demonstrated increased supraglottal activity (i.e., ventricular fold constriction) during stroboscopic evaluation. Significant differences compared to normative data were found in many aerodynamic and acoustic parameters. A substantial proportion (27%) of patients reported significant voice handicap. Younger patients reported greater handicap, and voice quality was worse with time. CONCLUSIONS: Significant objective and subjective changes in vocal function occur in patients radiated for nonlaryngeal head and neck malignancies. Young patients may have the worst impact, and vocal dysfunction may increase with time. A prospective study of this patient population should include a baseline voice quality assessment.

Hyperbaric oxygen corrects sacral plexopathy due to osteoradionecrosis appearing 15 years after pelvic irradiation.

In 1982, a 55-year-old woman was treated by total cystectomy and adjuvant radiotherapy/chemotherapy for a leiomyosarcoma of the bladder. Fifteen years later she presented with symptoms and signs of sacral plexopathy. Investigations revealed osteoradionecrosis of the sacrum. Hyperbaric oxygen therapy (HBO2) was instituted and progressive resolution of the neurological complaints followed. HBO2 should be considered when managing late-onset sequelae in previously irradiated patients.

Tumour volume: implications in T2/T3 glottic/supraglottic squamous cell carcinoma.

OBJECTIVE: In this study, tumour volume was investigated to determine if it predicts locoregional control of T2/T3 glottic/supraglottic laryngeal carcinoma treated with radiotherapy or surgery. The effect of radiotherapy dosage was also assessed in those patients treated with primary radiotherapy. The ability to identify a subset of patients suitable for primary radiotherapy and, hence, voice preservation based on pretreatment computerized axial tomography (CT) would be valuable. METHOD: The charts of 55 patients referred to the London Regional Cancer Centre (LRCC) between 1988 to 1994 were reviewed. Each presented with a previously untreated T2 or T3 squamous cell carcinoma (SCC) of either the glottic or supraglottic larynx. Tumour volume was calculated from pretreatment CT scans by observers unaware of the clinical data associated with each radiograph. Wilcoxon t test and univariate and multivariate Cox regression analyses were performed. RESULTS: Mean tumour volume differed between those patients treated with radiotherapy and those treated surgically (4.5 cm3 and 11 cm3, respectively; p < .01). Mean tumour volume also differed between T2 and T3 tumours in the primary radiotherapy group (3.8 cm3 and 9.3 cm3, respectively; p < .01). Tumour volume > 4.0 cm3 was a significant predicator of local failure in T2 laryngeal tumours treated with radiotherapy (p < .05). This volume effect was not abolished with increasing radiotherapy dosage. Tumour volume was not a significant predictor of local control in the T3 tumours treated with radiotherapy or when all tumours, irrespective of T stage, that were treated with radiotherapy were considered together. There was no similar volume effect found in the surgical group. CONCLUSIONS: Tumour volume > 4 cm3 predicts local failure in T2 laryngeal tumours treated with radiotherapy regardless of radiotherapy dosage. This volume effect is not seen in those tumours treated with surgery. Inclusion of tumour volume data may eventually augment our current classification system.

Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients.

PURPOSE: A retrospective review of patients with Stage I and II seminoma treated at a regional cancer center was performed to assess the long term efficacy and toxicity associated with post operative radiotherapy. METHODS AND MATERIALS: Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. RESULTS: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. No prognostic factors associated with increased risk of late toxicity or second malignancy were identified, likely a consequence of the small number of these events. CONCLUSION: Survival and toxicity were comparable to that reported in the literature. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma.

Epithelioid leiomyosarcoma of the larynx.

BACKGROUND: Tumors of smooth muscle origin are rare in the upper aerodigestive tract, due to the paucity of smooth muscle in the area. A review of the literature revealed 34 reported cases of leiomyoma, 9 cases of leiomyosarcoma, and only 2 cases of epithelioid leiomyoma arising in the larynx. METHODS: A case report of an epithelioid leiomyosarcoma arising in the right piriform fossa of a 38-year-old man is presented. RESULTS: The tumor was treated with conservative surgical resection and postoperative radiotherapy. There was no evidence of locoregional recurrence 2 years postsurgery, and laryngeal function was preserved. CONCLUSIONS: To our knowledge, this is the third case of a laryngeal epithelioid smooth muscle tumor to be reported in the world literature and the only documentation of an epithelioid leiomyosarcoma arising in the larynx.

Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study.

BACKGROUND AND OBJECTIVES: The commonest site of local breast recurrence after breast conservation surgery is the primary tumor bed. We have tested the feasibility of outpatient high dose rate brachytherapy to the primary tumor bed as the only radiation. Our technique relies on the placement of surgical clips to mark the tumor bed. METHODS: Between March 1992 and January 1996, 39 patients with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13 patients had intraoperative implantation of the breast. The remaining 26 patients had outpatient postoperative implantation under general anesthesia (2 patients) or local anaesthesia (24 patients). High dose rate brachytherapy was given twice daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7 days. RESULTS: Three patients had mild clinical cellulitis responding to oral antibiotics. One patient had a small sinus in the lumpectomy scar requiring local excision to heal. Four patients developed fat necrosis at the lumpectomy site at 4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy. Patient rated satisfaction with treatment was high. At a median followup of 20 months, one infield local recurrence has been salvaged by wider resection and postoperative conventional external beam radiation. CONCLUSIONS: Except for fat necrosis, which may be associated with this technique, complications have been minimal. Outpatient implantation under local anesthesia is feasible. Longer followup is required to establish the local control rates.

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant systemic therapy alone: patterns of recurrence.

PURPOSE: Prognostic factors for locoregional failure have been poorly documented. The purpose of this retrospective review is to examine the patterns of failure of 320 patients with Stage II or III axillary node-positive breast cancer who received adjuvant chemotherapy without locoregional radiation. METHODS AND MATERIALS: The records of 735 patients who were referred to the London Regional Cancer Centre between 1980 and 1989 with a diagnosis of Stage II or III breast cancer were reviewed. Three hundred and twenty patients were identified who underwent segmental mastectomy with axillary dissection or modified radical mastectomy and adjuvant chemotherapy without adjuvant locoregional radiation. Seventy-one percent of these patients had undergone a modified radical mastectomy, 40% had T1 tumors, 49% T2, and 11% T3. Resection margins were positive in 13 patients. The median number of axillary nodes removed was 11. Fifty-four percent had one to three positive axillary nodes, 27% had four to seven positive nodes, and 19% had in excess of seven positive nodes. RESULTS: Median follow-up for the 320 patients was 77 months. One hundred and fourteen patients developed a locoregional recurrence as the site of first relapse (31 in the intact breast, 29 on the chest wall, 21 in the axilla, 22 in the supraclavicular fossa, 1 in the internal mammary chain, and 10 in multiple sites). Thirty-three percent of segmental mastectomy patients and 13% of modified radical mastectomy patients developed local recurrence. Seven percent of patients recurred in axillary or supraclavicular nodes each. Factors with regard to locoregional recurrence which on univariate analysis were significant included type of mastectomy (i.e., segmental vs. modified radical), size of primary tumor, positive resection margins, and percentage of ideal chemotherapy dose intensity (< 66% vs. > or = 66%). After multivariate analysis, only type of mastectomy, size of primary tumor, and percentage of ideal chemotherapy dose intensity retained significance. The number of positive axillary nodes was not a significant factor. Number of positive axillary nodes plus the above four clinical factors were analyzed in terms of regional recurrence specifically. By univariate and multivariate analysis, only size of primary tumor retained significance. Again, the number of positive axillary nodes was not a relevant factor. CONCLUSION: Patients receiving adjuvant chemotherapy who are at high risk of locoregional recurrence include those who undergo segmental mastectomy and those with larger tumors (> 5 cm in diameter). Breast or chest wall radiation is recommended for these groups. Supraclavicular radiation is recommended for patients with tumors larger than 5 cm in diameter. Axillary recurrences were relatively infrequent in patients who had undergone an adequate Level I and II axillary dissection, and therefore, axillary radiation was not recommended.