Shigehiko Kuribayashi

Postoperative Radiation Protocol for Keloids and Hypertrophic Scars : Statistical Analysis of 370 Sites Followed for Over 18 Months

Background:Before 2002, keloids and intractable hypertrophic scars were treated at our facility with postoperative irradiation of 15 Gy (the traditional protocol). Analysis of the therapeutic outcomes of patients treated with this protocol showed that the recurrence rates of keloids and intractable hypertrophic scars in the anterior chest wall, as well as the scapular and suprapubic regions, were statistically higher than at other sites, while the recurrence rates in earlobes were lower. Thus, we customized doses for various sites. This report describes our trial of postoperative radiation therapy. Methods:Between January 2002 and September 2004, 109 patients with 121 keloid and intractable hypertrophic scar sites were treated with surgical excision following the new protocol: electron-beam irradiation at total doses of 10, 15, or 20 Gy, depending on the site. The recurrence rates and toxicities were historically followed in 218 patients with 249 keloid and intractable hypertrophic scar sites treated with the old protocol of surgical removal followed by irradiation at 15 Gy (without variation by site). The minimal follow-up time was 18 months. Statistical analysis was performed using Fisher exact probability test. Results:Total recurrence rates were 29.3% before 2002 and 14.0% after 2003. The recurrence rate in the anterior chest wall was statistically reduced. Outcomes of earlobe did not differ between irradiation with 15 Gy or 10 Gy. Conclusions:Keloids and intractable hypertrophic scars should be treated with dose protocols customized by site. Our results suggest that keloid and intractable hypertrophic scar sites with a high risk of recurrence should be treated with 20 Gy in 4 fractions over 4 days and that earlobe should be treated with 10 Gy in 2 fractions over 2 days.

Keloids and Hypertrophic Scars Can Now Be Cured Completely: Recent Progress in Our Understanding of the Pathogenesis of Keloids and Hypertrophic Scars and the Most Promising Current Therapeutic Strategy.

Keloids and hypertrophic scars are fibroproliferative disorders of the skin that are caused by abnormal healing of injured or irritated skin. It is possible that they are both manifestations of the same fibroproliferative skin disorder and just differ in terms of the intensity and duration of inflammation. These features may in turn be influenced by genetic, systemic, and local risk factors. Genetic factors may include single nucleotide polymorphisms, while systemic factors may include hypertension, pregnancy, hormones, and cytokines. The most important local factor is tension on the scar. Over the past 10 years, our understanding of the pathogenesis of keloids and hypertrophic scars has improved markedly. As a result, these previously intractable scars are now regarded as being treatable. There are many therapeutic options, including surgery, radiation, corticosteroids, 5-fluorouracil, cryotherapy, laser therapy, anti-allergy agents, anti-inflammatory agents, bleaching creams and make-up therapies. However, at present, we believe that the following combination of three therapies most reliably achieves a complete cure: surgery, followed by radiation and the use of steroid tape/plaster.

Utility of Sonography for Evaluation of Clinical T1 and T2 Glottic Carcinoma

Objective. The aim of this study was to evaluate the prognostic impact of sonographically determined tumor features in relation to local control of clinical T1 and T2 glottic carcinoma treated by definitive radiation therapy. Methods. Between 1999 and 2005, 72 patients with T1 and T2 glottic carcinoma were evaluated by percutaneous sonography in terms of tumor detectability, maximum tumor dimension, involvement of the anterior commissure, presence of supraglottic, subglottic, or paraglottic spread, and thyroid cartilage invasion. Factor analyses for local control included clinical features, sonographic findings, and treatment factors. Results. Forty‐one lesions (57%) were detected as hypoechoic masses on sonography. For detectable T2 tumors, sonographic and laryngoscopic findings were in agreement in all cases with respect to spread to anatomic subsites. The 3‐year local control rate with radiation therapy alone was 82%. Univariate analysis of the sonographic characteristics revealed that the maximum tumor dimension and thyroid cartilage invasion predicted a loss of local control, whereas none of the clinical or treatment characteristics was significant. Multivariate analysis showed that thyroid cartilage invasion was an independent negative prognostic factor for local control. Conclusions. Sonography provides information about the likely outcome of radiation therapy for patients with clinical T2 glottic carcinoma, although its utility for T1 lesions is not proven. Thyroid cartilage invasion may be an independent negative predictor of the outcome.

Advanced therapeutic strategy for radiation-induced osteosarcoma in the skull base: a case report and review

A review of patients with skull base osteosarcoma secondary to radiation (radiation-induced osteosarcoma: RIOS) of the pituitary tumor shows the mean survival of approximately 7 months (2 weeks – 16 months). This warning prognosis seems to stem from two factors, 1) the anatomical complexity of the skull base for total resection of the tumor, and 2) standard adjuvant therapies for the tumor yet to be established. Contrary to the general belief, the authors report an unusually long survival of a 75-year-old woman with a history of osteosarcoma that developed in the same sequence 20 years after pituitary tumor radiation. On her recent admission, she complained of frontal headaches and MRI studies showed a tumor in the sphenoid sinus. Endoscopic trans-nasal tumor removal allowed for histological diagnosis of an osteosarcoma. However, further rapid tumor growth necessitated a radical tumor resection followed by a combined chemotherapy with ifosfamide, cisplatin, and etoposide (ICE). Despite temporary suppression of the tumor growth, the chemotherapy was discontinued due to severe pancytopenia that occurred after three courses of treatment. Shortly after the discontinuation of ICE therapy, the tumor size increased again rapidly, requiring a novel radiation therapy, Cyber-knife treatment. Following this radiation, the tumor growth was arrested, and the patient remains healthy without neurological symptoms over 24 months. The outcome of Cyber-knife in this case suggests that this specific therapy must be considered for the unresectable skull base RIOS.

Reply: Analysis of the Surgical Treatments of 63 Keloids on the Cartilaginous Part of the Auricle: Effectiveness of the Core Excision Method.

Background: Treatments for keloids on the cartilaginous part of the auricle (i.e., the upper part of the ear excluding the earlobe) include surgical excision, cryosurgery, postoperative radiation therapy, steroid injection, taping stabilization, and pressure therapy. However, to date, there is no universally accepted treatment strategy for auricle keloids. Methods: In this retrospective cohort study, the 63 primary auricle keloids in all 57 patients who underwent surgery from 2006 to 2012 were included. Mild scars such as hypertrophic scars were excluded. All 63 scars were treated with surgery, namely, total excision or intralesional excision (core excision method), and postoperative adjuvant radiation therapy and self-managed scar stabilization with surgical tape. The postsurgical radiation therapy consisted of 15 Gy administered in three fractions over 3 days. The recurrence rates associated with the two surgical methods over 18 months of follow-up were recorded. Results: Of the 57 patients, 91.2 percent were women. Of the 63 lesions, 95.2 percent and 4.8 percent were caused by piercing and trauma, respectively. All were primary keloids. Before 2009, all lesions (n = 37) were treated by total excision. After 2009, all lesions (n = 26) were treated by core excision. These methods were associated with recurrence rates of 8.1 percent and 0 percent, respectively, although this difference did not achieve statistical significance (p > 0.05). The overall recurrence rate was 4.8 percent. Complications such as wound dehiscence and pigmentation during the 18-month follow-up period were not observed. Conclusion: Auricle keloids can be treated by customized plans consisting of appropriate surgical modalities, postoperative radiotherapy, and self-management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy

Background:Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation.Methods:We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed.Results:Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed.Conclusions:Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes.