Avoidance or adaptation of radiotherapy in patients with cancer with Li-Fraumeni and heritable TP53-related cancer syndromes.

The management of patients with cancer and Li-Fraumeni or heritable TP53-related cancer syndromes is complex because of their increased risk of developing second malignant neoplasms after genotoxic stresses such as systemic treatments or radiotherapy (radiosusceptibility). Clinical decision making also integrates the risks of normal tissue toxicity and sequelae (radiosensitivity) and tumour response to radiotherapy (radioresistance and radiocurability). Radiotherapy should be avoided in patients with cancer and Li-Fraumeni or heritable TP53 cancer-related syndromes, but overall prognosis might be poor without radiotherapy: radioresistance in these patients seems similar to or worse than that of the general population. Radiosensitivity in germline TP53 variant carriers seems similar to that in the general population. The risk of second malignant neoplasms according to germline TP53 variant and the patient's overall oncological prognosis should be assessed during specialised multidisciplinary staff meetings. Radiotherapy should be avoided whenever other similarly curative treatment options are available. In other cases, it should be adapted to minimise the risk of second malignant neoplasms in patients who still require radiotherapy despite its genotoxicity, in view of its potential benefit. Adaptations might be achieved through the reduction of irradiated volumes using proton therapy, non-ionising diagnostic procedures, image guidance, and minimal stray radiation. Non-ionising imaging should become more systematic. Radiotherapy approaches that might result in a lower probability of misrepaired DNA damage (eg, particle therapy biology and tumour targeting) are an area of investigation.

Four generations of SDHB-related disease: complexities in management.

SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4), which is associated with predominantly extra-adrenal disease and has high metastatic rates. Despite the lower penetrance rates in carriers of SDHB mutations compared to mutations in other paraganglioma susceptibility genes, the aggressive behavior of SDHB-linked disease warrants intensive surveillance to identify and resect tumors early. Patients with similar SDHB genotypes in whom the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors can arise in various locations, and management can be considerably different, depending on tumor site and pathology. We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management.

Palliation of Extensive Metastatic Bone Disease With 223Ra-Dichloride α-Particle Therapy in a Patient With Malignant Hereditary Paraganglioma-Pheochromocytoma Syndrome With SDHB Mutation.

A 26-year-old woman with a 5-year history of metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome with SDHB mutation, who had failed multiple treatment regimens and had transfusion dependent pancytopenia, presented with progressive liver and bone metastases. She was unable to sleep due to painful skull metastases and had severe weakness in her extremities that limited her mobility and daily activities. She was treated with 2 doses of Ra-dichloride (Xofigo, Ra) and had a dramatic improvement in pain control, mobility, and overall quality of life for 8 weeks, before passing away from pulmonary hemorrhage.

Additive effect of propranolol and pulsed dye laser for infantile hemangioma.

The combination of propranolol and pulsed dye laser for the treatment of infantile hemangiomas may be superior to either alone. This case report illustrates the additive effect of propranolol and pulsed dye laser for an infantile hemangioma in a high-risk location. Although thorough clinical trials are needed, combination therapy for infantile hemangiomas may prove to be optimal for efficacy.

Clinical and mutation analysis of four Chinese families with von Hippel-Lindau disease

OBJECTIVE: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposed to the development of tumors in a variety of body organs. The major etiopathogenesis of VHL is a mutation of the VHL tumor-suppressor gene on the short arm of chromosome 3 (3p25-26). We report on the clinical and molecular features of four Chinese kindreds with VHL disease. MATERIALS AND METHODS: The VHL gene was screened for mutation using a direct DNA sequencing analysis and a multiplex ligation-dependent probe amplification (MLPA) for 44 volunteers from these four families. Any unaffected person, with germline VHL gene mutation, was required to undergo further examination, surveillance and treatment. RESULTS: The main lesions and the average diagnostic year of the 20 patients were central nervous system hemangioblastoma (60 %, 34.92 years), renal lesion (60 %, 39.08 years), pancreatic lesion (60 %, 37.67 years), adrenal pheochromocytoma (25 %, 37.8 years) and retinal hemangioblastoma (10 %, 25.5 years). Direct sequencing detected nucleotide substitutions or small deletions in three families and MLPA revealed exon 1 deletion in family A. The five asymptomatic patients were initially diagnosed by genetic analysis and verified radiologically or surgically. CONCLUSIONS: The spectrum of clinical manifestation of VHL in the mainland Chinese population is similar to the observation in Western kindreds. Genetic testing, which plays a crucial role in early diagnosis asymptomatic patients, is obviously superior to clinical informations when diagnosing VHL disease. The members of VHL disease family may benefit from pedigree study, genetic testing, periodic follow-up, early diagnosis and prompt treatment (AU)

Palliative radiation therapy in a dog with malignant trichoepithelioma.

An 11-year-old male Bearded Collie was brought to the Gifu University Animal Medical Centre with a skin mass on the lateral right thigh. Physical examination revealed a 30 × 65-mm oval mass with an alopecic and ulcerated surface. Histopathology of the surgically excised sample confirmed malignant trichoepithelioma. Five months after the surgery, the dog experienced lumbar pain resulting from metastasis to the lumbar vertebrae. Radiation therapy (RT) was performed and it alleviated the lumbar pain. Nine months after the surgery, multiple skin metastases were identified. RT was performed at each occurrence, which reduced the size of each tumour and resulted in a partial response; however, systemic metastasis occurred and the dog died 17 months after the initial surgery. Canine malignant trichoepithelioma is a rare tumour, so an effective treatment has not been determined. Data from our case study indicate that RT has potential for pain control of primary and metastatic malignant trichoepithelioma.

Severe exacerbation of multiple self-healing squamous epithelioma (Ferguson-Smith disease) with radiotherapy, which was successfully treated with acitretin.

We describe the challenging case of a patient presenting with extensive, eruptive mid-facial squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) consequent to radiotherapy. Our patient had a personal and family history of multiple KAs and SCCs. Multiple self-healing squamous epithelioma, otherwise known as Ferguson-Smith disease, was diagnosed. This case presented a therapeutic challenge to preserve tissue and avoid severe facial disfigurement. We found oral acitretin to be the treatment of choice.

Radiation-sensitive genetically susceptible pediatric sub-populations.

Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation.

Brooke-Spiegler syndrome: treatment with laser ablation.

Brooke-Spiegler syndrome is a rare genetic condition associated with adnexal and epidermal tumours. Facial trichoepitheliomas and cylindromas are particularly distressing to sufferers. Conventional treatment can be followed by recurrence. We report a case with disfiguring trichoepithelioma treated with erbium:Yag and CO2 laser, achieving a good cosmetic result without recurrence after 2 years. Brooke-Spiegler syndrome and its treatment are reviewed.

New approaches to surgery for breast cancer.

The surgical management of breast cancer is rapidly evolving towards less invasive procedures. Alternative biopsy techniques, including fine-needle aspiration and core needle biopsy, are replacing excisional biopsy as the treatment standard. Breast conservation therapy is now widely used in place of mastectomy, both for small tumors and for larger tumors that have been downstaged through induction chemotherapy. Less invasive procedures for axillary treatment such as lymphatic mapping and sentinel lymph-node biopsy are being explored in an effort to avoid the morbidity associated with axillary lymph-node dissection. For women who still prefer or need to receive a mastectomy, immediate breast reconstruction with autologous tissue provides an excellent cosmetic outcome that is oncologically sound. This is especially appealing to high-risk women who opt to have a prophylactic mastectomy. High-risk women are also being offered the option of receiving chemopreventive treatment that may reduce their lifetime risk of cancer by almost 50%. These new, less invasive approaches require the close cooperation of a team of physicians,including surgeons, pathologists, radiologists, and medical and radiation oncologists.

Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation.

PURPOSE: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. METHODS AND MATERIALS: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. RESULTS: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T-stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. CONCLUSIONS: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in clinicopathological features, in response to treatment, or in ultimate outcome.