Intensity-modulated radiotherapy (55 Gy in 20 fractions) for high-grade laryngeal dysplasia: report of acute toxicity and functional outcome.

OBJECTIVE: Radiotherapy is an option to treat high-grade laryngeal dysplasia. This study aimed to evaluate the use of intensity-modulated radiotherapy, 55 Gy in 20 daily fractions, in treating this disease. METHODS: Acute toxicity was evaluated in all 14 patients treated. In 10 patients, functional voice outcome was measured using the Voice Handicap Index, and the Grade, Roughness, Breath, Asthenia, Strain ('GRBAS') scale. These measurements were performed pre-treatment and three months after intensity-modulated radiotherapy. RESULTS: All but one patient managed to complete radiotherapy. Acute toxicity was significant (one patient developed grade 4 and three patients developed grade 3 dysphagia). Four patients required hospital admission. In 9 out of 10 patients, radiotherapy improved voice quality. CONCLUSION: This radiotherapy regimen using intensity-modulated radiotherapy for laryngeal dysplasia is feasible and provided excellent functional outcome, but acute toxicity was significant. Dose de-escalation can be considered in the framework of clinical trials.

Outcomes of Treating Early Glottic Neoplasms With a Potassium Titanyl Phosphate Laser.

OBJECTIVES:: The aim of this study was to assess the outcome of treating glottic dysplasia and early squamous cell carcinoma (SCC) with potassium titanyl phosphate (KTP) photoangiolytic laser ablation. METHODS:: Patient demographics, comorbidities, and tumor characteristics were recorded. Perceptual, patient-reported, and objective voice outcomes were assessed. Use of treatment modalities in addition to the KTP laser, development of locoregional or metastatic SCC, and overall survival were recorded. RESULTS:: There were 23 patients with glottic dysplasia and 18 patients with glottic SCC. Mean age at treatment was 69 years. Most patients (95%) were male. Posttreatment fundamental frequency fell from 132 ± 35 to 116 ± 24 Hz ( P = .03). Overall, 61% of patients achieved a normal voice. There was a learning-curve, and most treatment failures occurred in the first half of the series. Five-year KTP-only disease-control rates were 87.1% and 53.5% for dysplasia and malignancy, respectively. Five-year overall survival was 56%, with no laryngectomies or deaths due to SCC. CONCLUSIONS:: Ablating dysplasia and early glottic cancer using a KTP laser is a viable treatment option. It has a learning curve and a failure rate but, in this series, no ultimate loss of oncologic control. Its introduction into clinical practice should be managed carefully in the context of multidisciplinary cancer care. LEVEL OF EVIDENCE:: 4.

Fluorescence spectroscopic study on malignant and premalignant oral mucosa of patients undergoing treatment: An observational prospective study.

BACKGROUND: To evaluate the changes of oral mucosa in malignancy and pre-malignant oral conditions using fluorescence spectroscopy during various phases of treatment. MATERIAL AND METHODS: The study involved patients of squamous cell carcinoma of the oral cavity and the premalignant lesions coming for the follow up/post-operative radiotherapy. The autofluorescence spectra were recorded in vivo using a Nitrogen laser based fluorimeter. Three sites of each patient were examined-right & the left buccal mucosa and the tongue. For a given pathology, spectra from all the individuals were grouped and mean spectra after different radiation cycles were compared. The quantitative analysis of the spectra involved extraction of diagnostically relevant spectral information through Maximum Representation and Discrimination Feature. RESULTS: As different patients had different response to the radiation, it was difficult to visualize any particular trend with increased number of radiation cycles. However, for a given pathology and an individual, when mean spectra after different radiation cycles and surgery were compared, the observation was: Intensity of the 460 nm fluorescence band for each pathology was increased with the number of radiation cycle. That had indicated tissue was being reverted back to its grossly normal features. As 460 nm fluorescence spike was a standard spectra for normal mucosa. CONCLUSION: The results strengthened the hypothesis that fluorescence spectroscopy has considerable potential for use as a tool to evaluate the response to treatment in oral malignancy. These spectra of radiotherapy and surgically treated patients can be used as standards for treated patients in further studies.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r > 0.87 and p-values >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Problems and complications of full-face carbon dioxide laser resurfacing for pathological lesions of the skin.

OBJECTIVE: Facial resurfacing with a CO2 laser has been used for treatment of pathologic lesions and for cosmetic purposes. Postoperative complications and problems after laser resurfacing include infections, acneiform lesions, and pigment changes. This retrospective study describes the most common problems and complications in 105 patients and assesses postoperative pain in 38 patients. STUDY DESIGN: All patients received CO2 laser resurfacing for treatment of malignant/premalignant lesions and had postoperative follow-up to assess problems and complications. Some had follow-up to assess postoperative pain. All patients had Fitzpatrick I-III skin types and underwent the same perioperative care regimen. RESULTS: There were 11 problems and 2 complications. Problems included infection, acneiform lesion/milia, and uncontrolled postoperative pain. Complications included hyperpigmentation. Among the postoperative pain group, 53% reported no pain and the rest had mild or moderate pain. CONCLUSION: Complications are rare. Infection and acneiform lesions/milia were the most common problems, as previously reported. Most patients do not experience postoperative pain.

Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.

OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

BACKGROUND: We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. MATERIAL AND METHODS: Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. RESULTS: Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. CONCLUSION: Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

Management of premalignant lesions of the larynx.

Premalignant lesions of the laryngeal epithelium most commonly involve the glottis. Abnormal appearing mucosal lesions may warrant biopsy for histologic review before an assessment can be made regarding their risk for malignant transformation. Although higher degrees of dysplasia portend a greater chance for malignant transformation, findings of dysplasia or carcinoma in situ should prompt ablative therapy followed by surveillance for recurrence or progression. Risk factor modification remains important not only as a primary prevention strategy, but also to reduce the risk of progression to invasive carcinoma. We review the current evidence pertaining to the work-up and management of premalignant epithelial lesions of the larynx. Surgical excision continues to be the treatment of choice. Alternative therapies like photodynamic therapy and radiation may be employed in selected patients when surgical therapy is not the best option.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model.

OBJECTIVES: Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model. MATERIALS AND METHODS: Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. RESULTS: A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. CONCLUSION: BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue.

Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval.

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10+BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10+BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.

Reversing precancerous actinic damage by mixing wavelengths (1064 nm, 532 nm).

BACKGROUND: Premalignancies resulting from photodamage, such as actinic keratosis and carcinoma in situ, can be treated with various modalities. Most of these treatments may reverse or treat these conditions although they often involve considerable skin irritation over a long period of time, are very uncomfortable for the patients or they need many office visits and sometimes are very expensive, such as photodynamic therapy (PDT). OBJECTIVE: To study the effectiveness of a mixed session of Q-switched KTP 532 nm and Nd:YAG 1064 nm laser treatment on precancerous lesions resulting from solar damage. METHODS: Ten patients with long-standing actinic damage/keratosis or carcinoma in situ were subjected to only one session of mixed Q-switched KTP 532 nm and Nd:YAG 1064 nm laser treatment. Lesions were evenly and repeatedly scanned with both wavelengths until light pain or purpura presented. RESULTS: All patients responded extremely well within a period of 20 days, with just one session, with virtually no pain, minimum irritation, no down time at all and excellent cosmetic outcome. CONCLUSION: The use of a mixed Q-switched 532 nm and Nd:YAG 1064 nm laser session seems to be ideal for treating precancerous lesions resulting from photodamage since it can be a fast, painless and simple office procedure with no down time and minimum discomfort for the patient. This method proves to be much more selective than traditional intense pulse light (IPL) photorejuvenation.

[Malignant epibulbar tumours: new strategies in diagnostics and therapy]. / Maligne epibulbäre Tumoren: Neue Strategien in Diagnostik und Therapie.

In this article we discuss the complex diagnostic approaches and therapeutic options for the most important conjunctival malignancies. Conjunctival melanoma can be a diagnostic challenge as it can be difficult to distinguish from benign melanocytic conjunctival tumours. Complete surgical excision accompanied by a coherent adjuvant concept is the key for a curative therapy. Moderate and severe conjunctival intraepithelial neoplasias (CIN) are precancerous lesions and can progress to invasive squamous cell carcinoma. The involvement of large parts of the ocular surface can prevent an R 0-resection. Adjuvant therapeutic concepts are therefore especially important to gain tumour control and preserve the function of the affected eye. Lymphomas are the most common malignant primary tumours of the orbit and ocular adnexa. They can present as primary or secondary tumours of the conjunctiva, the lacrimal gland, the orbital fat, the eye lid or the lacrimal sac. The most common manifestation site of ocular MALT lymphoma is the conjunctiva with 20 - 33 % of all epibulbar lymphomas. More than 75 % of ocular lymphoma patients develop only one lymphomatous lesion. Immunophenotyping allows the exact differentiation between the lymphoma entities. Infectious agents (e.g., Chlamydia psittaci) seem to play a role in the pathogenesis. An overview over radiotherapeutic approaches that are conclusively applicable at the conjunctiva completes the article.

Monomorphic epithelial proliferations of the breast: a possible precursor lesion associated with ipsilateral breast failure after breast conserving therapy in patients with negative lumpectomy margins.

BACKGROUND: It is generally believed that ipsilateral breast failures (IBFs) after breast-conserving therapy (BCT) develop from incompletely eradicated carcinoma. We previously suggested that monomorphic epithelial proliferations (MEPs) in the breast may be a pool of partially transformed clones from which breast carcinomas can arise and that radiation therapy (RT) may also reduce the risk of IBF by eradicating MEPs. We examined salvage mastectomy specimens in patients experiencing an IBF to define the relationship between MEPs and IBFs and an additional potential mechanism for IBF risk reduction by RT. METHODS AND MATERIALS: The location, number, and distribution of radiation changes and MEPs relative to 51 IBFs were mapped in salvage mastectomy specimens from BCT patients with adequately excised, initial carcinomas (negative lumpectomy margins). RESULTS: All 51 salvage mastectomies had diffuse, late radiation changes. None had active fibrocystic lesions. MEPs were predominantly located in the immediate vicinity of the IBFs. A mean of 39% of MEP cases were located within the IBF, 46% were located within 2 cm of the IBF, and 14% were 2-3 cm from the IBF. CONCLUSIONS: MEPs appear to be a pool of partially transformed precursor lesions that can give rise to ductal carcinoma in situ and invasive carcinomas (CAs). Many IBFs may arise from MEPs that reemerge after RT. Radiation may also reduce IBF risk after BCT (including in patients with negative margins) by primarily eradicating MEPs.

Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumors of the hamster cheek pouch.

Mast cell (MC) activation in the hamster cheek pouch cancerization model is associated with the increase in tumor cell proliferation, mediated in turn by tryptase, a protease released from mast cell granules after activation. Tryptase induces tumor cell proliferation through the activation of PAR-2 (protease activated receptor-2) on the plasma membrane of carcinoma cells. The therapeutic success of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) in tumor control in the hamster cheek pouch oral cancer model has been previously reported by our laboratory. Early effects of BPA-BNCT on tumors of the hamster cheek pouch include a reduction in DNA-synthesis with the concomitant decrease in the proliferation of malignant cells. The aim of the present study was to investigate the early histological changes in mast cells after BPA-BNCT in tumors and premalignant tissue of the hamster cheek pouch. Tumor-bearing pouches were treated with BPA-BNCT or beam only (neutron irradiation without prior administration of the boron compound) and sacrificed 1day after treatment. The samples were fixed in Carnoy fixative and stained with alcian blue-safranin to identify all the populations of mast cells. Total, active and inactive mast cells (MC) were counted in the connective tissue and the adventitious tissue underlying the pouch wall and at the base of the tumors in pouches treated with BPA-BNCT, in keeping with a previously described technique. BPA-BNCT induced a marked reduction in the total number of mast cells in the pouch (p<0.05). This reduction in the total number of mast cells was due to a reduction in mast cells at the base of the tumor (p<0.005) and it occurred at the expense of the active mast cells (p<0.05). A slight reduction that did not reach statistical significance also occurred in the amount of mast cells in the pouch wall (that corresponds to the premalignant tissue in tumor-bearing pouches), and in the adventitious tissue. In this case the reduction was seen in the inactive population. Both BPA-BNCT and beam only elicited a qualitative change in the secretion modality of the granule content. Although further studies are needed to evaluate the subcellular effect of BNCT on mast cell granule secretion, the reduction in cell proliferation induced by BPA-BNCT would be partially due to the decrease in total mast cells in the hamster check pouch.

[Neoadjuvant therapy in the upper gastro-intestinal tract. Modern strategies for Barrett's cancer]. / Neoadjuvante Therapie im oberen Gastrointestinaltrakt. Aktuelle Konzepte beim Barrett-Karzinom.

While primary surgical resection with systematic lymphadenectomy remains the treatment of choice for locoregional Barrett's cancer, neoadjuvant chemotherapy is an increasingly accepted treatment modality for patients with locally advanced tumors and patients with extensive lymphatic spread. In contrast to neoadjuvant radiochemotherapy preoperative chemotherapy alone does not seem to increase peri-operative complications and mortality. Responders to pre-operative treatment clearly have a survival advantage as compared to those who do not respond. The use of positron emission tomography to measure changes in glucose metabolism of the primary tumor can predict response early after initiation of neoadjuvant chemotherapy and thus help to select patients who will or will not benefit from this approach. The best treatment strategy for non-responders to neoadjuvant therapy remains to be defined.

Reduced risk of head and neck second primary tumors after radiotherapy.

BACKGROUND AND PURPOSE: With radiotherapy of primary tumors of the head and neck, a significant dose reaches the surrounding mucosa. The field cancerization and second field tumor theories state that premalignant lesions are present in the mucosa even at the time of primary tumor treatment. We tested the hypothesis that exposure to irradiation stabilizes subclinical premalignant lesions. This would reduce the rate of second primary tumors in the upper aerodigestive tract (UADT). MATERIALS AND METHODS: The cohort consisted of 346 patients treated for small localized squamous cell carcinoma of the oral cavity (T1-2, N0, and M0). The rate of UADT second primary tumors was compared between 247 patients exposed to radiation (case subjects) and 99 patients unexposed to radiation (control subjects). RESULTS: Median time to UADT second primary tumor was 8.6 years for irradiated patients and 3.9 years for controls (p=0.007). Through the first 5 years after the treatment of the primary tumor, the relative risk of developing a new UADT tumor for irradiated patients compared to controls was 0.12 (p<0.001). After 5 years the risk increased for irradiated cases. A corresponding change in risk was not found for controls. CONCLUSIONS: A slower rate of second primary tumors was seen within UADT mucosa exposed to irradiation. This could suggest a preventive effect by radiation on malignant transformation of subclinical premalignant foci.

Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: an experimental study that supports a potential new application of BNCT.

We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

A study of actinic cheilitis treatment by two low-morbidity CO2 laser vaporization one-pass protocols.

Therapeutic approaches to chronic actinic cheilitis focus on the removal or destruction of diseased epithelium. The CO(2) laser has become an important therapeutic alternative, achieving clinical resolution in around 90% of patients. Although many laser physical parameters have been reported, some are known for their low potential for scar induction without compromising the success of the results. The aim of this clinicohistological study was to compare the therapeutic responses to two low-morbidity protocols involving a single laser pass. A total of 40 patients with chronic multicentric and microscopically proven disease were randomly submitted to two conservative CO(2) laser protocols using a bilateral comparative model. The degree of histological atypia of the epithelium was determined in 26 patients both pre- and postoperatively for both protocols. Other histological phenomena were assessed in addition to this central analysis parameter. Clinical recurrence occurred in 12.5% of patients for each protocol, together with a significant reduction in the degree of epithelial atypia (p < 0.001), which was occasionally complete. However, no difference was found between the protocols (p > 0.05). Using these morphological parameters it was not possible to determine whether postoperative epithelial atypias in part of the sample were reactive or residual in nature. A few patients may show minor postoperative lesions. Due to their potential to achieve clinical and importantly microscopic resolution, the studied protocols may be used for mild through moderate dysplastic epithelium and clinically diffuse disease.

Controversies over the role of radiation therapy for ductal carcinoma in situ.

Ductal carcinoma in situ is a premalignant disease of the breast with a rapidly rising incidence. For women with localized ductal carcinoma in situ, randomized trials have shown that radiation therapy following conservative surgery lowers the relative risk of progression to invasive disease by 60%. Therefore, following conservative surgery, radiation therapy to the breast is generally considered a reasonable standard of care. However, several clinical trials have investigated the safety of conservative surgery alone without radiation for select women with small tumors of low histologic grade excised with widely negative margins. At present, results of these trials are conflicting, and, therefore, radiation therapy is generally recommended following conservative surgery, even for patients with favorable pathologic characteristics.

Effects of exposure of newborn patched1 heterozygous mice to GSM, 900 MHz.

Patched1 heterozygous knockout mice (Ptc1+/-), an animal model of multiorgan tumorigenesis in which ionizing radiation dramatically accelerates tumor development, were used to study the potential tumorigenic effects of electromagnetic fields (EMFs) on neonatal mice. Two hundred Ptc1+/- mice and their wild-type siblings were enrolled in this study. Newborn mice were exposed to 900 MHz radiofrequency radiation (average SAR: 0.4 W/kg for 5 days, 0.5 h twice a day) or were sham exposed. We found that RF EMFs simulating the Global System for Mobile Communications (GSM) did not affect the survival of the mice, because no statistically significant differences in survival were found between exposed and sham-exposed animals. Also, no effects attributable to radiofrequency radiation were observed on the incidence and histology of Ptc1-associated cerebellar tumors. Moreover, the skin phenotype was analyzed to look for proliferative effects of RF EMFs on the epidermal basal layer and for acceleration of preneoplastic lesions typical of the basal cell carcinoma phenotype of this model. We found no evidence of proliferative or promotional effects in the skin from neonatal exposure to radiofrequency radiation. Furthermore, no difference in Ptc1-associated rhabdomyosarcomas was detected between sham-exposed and exposed mice. Thus, under the experimental conditions tested, there was no evidence of life shortening or tumorigenic effects of neonatal exposure to GSM RF radiation in a highly tumor-susceptible mouse model.