Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults

Background

Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear.

Aim

The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012.

Results

MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30–36 Gy delivered in 6–10 weeks.

Conclusion

TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies.     

Effect of exposure method to Beauveria bassiana and conidia concentration on mortality, mycosis, and sporulation in cadavers of Chilo partellus (Lepidoptera: Pyralidae)

The effects of exposure methods, conidial concentrations, and temperature on mortality, mycosis and sporulation in second instar Chilo partellus cadavers infected by Beauveria bassiana was investigated in laboratory studies. Larvae directly sprayed with conidia, exposed to conidia-treated leaves, and dipped into conidial suspension resulted in high mortality (98-100%). The longest LT50 (3.5 days) and days to mortality (2.6 days) were observed in the treated-leaves exposure method. The shortest LT50 (1 day) and days to mortality (1 day) were recorded for the dipping method. With increasing conidial concentrations, there were decreasing LT50 and days to mortality. Larvae exposed to treated leaves and larvae directly sprayed with conidial suspensions produced high mycoses in cadavers. Exposure of larvae to treated-leaves resulted in high sporulation. At lower concentrations of conidia, both mycosis and sporulation in cadavers were high. The optimum temperature for mycosis was 20 and 15 degrees C for sporulation.     

Advantages and implications of high dose rate (HDR) total skin electron irradiation (TSEI) for the management of Mycosis Fungoides. Indian experience

Background

Mycosis Fungoides (MF) is an indolent lymphoproliferative disorder affecting dermis caused by abnormal proliferation of CD4+ T-cells. Radiation therapy is the most effective modality of treatment for MF which offers cure in limited stage disease and desirable palliation in advance stage disease. Treating entire skin having many curved surfaces and folds with radiation is the real challenge for the radiation oncologist. Many techniques, dose schedules and modifications in total skin electron irradiation (TSEI) have been tried since 1950s. TSEI treatment is a very time consuming, inconvenient and physically challenging to both patient as well as oncologist.

Aim

At our center TSEI was performed since 1983 with conventional linear accelerator where the treatment time was prolonged beyond two hours, which was very difficult or the patient, oncologist, technical officer and eating away the machine time hampering the treatment of other patients. From 1998 we shifted to high dose rate (HDR) mode, in order to bring down the treatment time of a single patient every day from two and half hour to 15 min. The reduction of treatment time increases patient compliance and at the same time saved machine time.

Materials and methods

Between 1998 and 2003, eleven pathological diagnosed MF patients were treated using HDR TSEI. All the patients were male between 40 and 70 years of age, who had the history of having the disease for 7–22 months. Four patients had T2 and seven patients had T3 stage disease with more than 90% skin surface involvement. TSEI was performed with 4 MeV electrons with a daily fraction size of 120 cGy to a total dose of 36 Gy. At the end of 36 Gy, boost dose of 10 Gy was delivered to self shielding regions like sole, scalp and perineum. Considering the treatment related toxicities and consequent treatment interruptions, in the first seven patients, the last four patients were treated using similar HDR TSEI technique with modified treatment schedule, where the treatment was given on an alternate day basis following 2nd week of initiation of treatment.

Results

The patients were followed over a period of 144 months with a median of 72 months. Nine patients are alive without any evidence of disease, one patient relapsed and one died due to progression of disease. The most common radiation related morbidities are erythema, skin blisters, various degree of desquamations, swelling of joints (specially small joints) etc. which are controlled by treatment interruptions and conservative measures. By modifying the treatment schedule, the incidence of toxicity as well as treatment interruptions were brought down.

Conclusions

We can conclude that HDR-TSEI is an excellent and safe therapeutic modality for the patients with MF both curative as well as palliative without any added toxicity profile, provided patient positioning is done properly.     

Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Recent reports indicate that loss of STAT4 expression is an important prognostic marker for CTCL progression and is associated with the acquisition of T helper 2 cell phenotype by malignant cells. However, little is known about the molecular mechanism behind the downregulation of STAT4 in this cancer. In the current work we test the expression of STAT4 and STAT6 via RT-PCR and/or Western Blot in CTCL lesional skin samples and in immortalized patient-derived cell lines. In these malignant cell lines we correlate the expression of STAT4 and STAT6 with the T helper (Th) phenotype markers and test the effect of Histone Deacetylase (HDAC) inhibitors and siRNA-mediated knock down of miR-155 on STAT4 expression. Our findings demonstrate that STAT4 expression correlates with Th1 phenotype, while STAT6 is associated with the Th2 phenotype. Our results further document that STAT4 and STAT6 genes are inversely regulated in CTCL. Treatment with HDAC inhibitors upregulates STAT4 expression, while at the same time decreases STAT6 expression in MyLa cells. Also, siRNA-mediated knock down of miR-155 leads to upregulation in STAT4 expression in MyLa cells. In summary, our results suggest that loss of STAT4 expression and associated switch to Th2 phenotype during Mycosis Fungoides progression may be driven via aberrant histone acetylation and/or upregulation of oncogenic miR-155 microRNA.     

Chrysosporium tropicum as a probable cause of mycosis of poultry in India

Chrysosporium tropicum was isolated from comb lesions in two different breeds of chickens in India and subcultures were shown to be pathogenic when inoculated onto prepared skin of guinea pigs. This report provides additional evidence to considerCh. tropicum as a pathogenic fungus and a probable cause of a dermatomycosis in chickens.     

A systematic review and meta-analysis of immune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?

Over the last decades, a revolution has occurred in oncology with the development of immune checkpoint inhibitors (ICIs). Following tremendous successes in solid tumors, interest has risen to explore these inhibitors in hematologic malignancies; while Hodgkin's lymphoma (HL) has shown overwhelming achievements, available data on different types of non-Hodgkin's lymphoma (NHL) vary considerably. To the best of our knowledge, no meta-analysis has assessed the efficacy and safety of ICI therapy in relapsed or refractory NHL patients. Meta-analysis of the included studies (n = 29) indicated PD-1 may probably be the more attractive ICI target rather than PD-L1 and CTLA-4 in NHL patients. Also, there is a plausible correlation between NHL subtypes and response to ICI therapy. While MF, ENKTL, RT, and PMBCL showed promising responses to ICI monotherapy, neither FL nor DLBCL had satisfactory responses; further necessitating novel strategies such as the application of ICIs in combination with other treatment strategies. Notably, among different combinations, BTK inhibitors showed an obvious improvement as compared to ICI monotherapy in both FL and DLBCL, however, the best results were obtained when ICI was combined with anti-CD20 monoclonal antibodies. Finally, while most NHL patients who received ICI treatment have experienced mild AEs, larger trials with long-term follow-up are required to confirm the safety, as well as the efficacy, of ICI therapy in NHL patients.     

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center

AimThe aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT).BackgroundPrimary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative.Materials and MethodsThis is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality.ResultsEight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (n = 5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12 Gy), 1 patient, the intermediate-dose RT scheme (24 Gy), and 2 patients, the conventional-dose RT scheme (36 Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6–8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months.ConclusionThis study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.