J.C. Yang

Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451.

Parameningeal Rhabdomyosarcoma: Outcomes and Opportunities

PURPOSE To examine patterns of failure in patients with parameningeal rhabdomyosarcoma (PM-RMS) treated with intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS Forty-seven patients with PM-RMS received chemotherapy and IMRT for definitive treatment. The median age was 9 years (range, 0.5-35 years). The high-risk features were as follows: 40% alveolar histology, 72% group III and 26% group IV disease, 57% either intracranial extension (ICE) (n=25) or cranial neuropathy (n=21). The median time to RT from the start of chemotherapy was 15 weeks (range, 2-54 weeks). Patients received 50.4 Gy in 1.8-Gy fractions to the primary tumor by use of IMRT. Thirteen patients aged≥14 years with alveolar histology received 36 Gy prophylactic nodal irradiation (PNI) to bilateral cervical nodes. Events were defined as local, regional (nodal), central nervous system (CNS), or distant failures. RESULTS With a median follow-up time of 3.3 years (range, 0.5-12.8 years), 18 patients experienced failure: 5 local, 2 regional, 6 distant, and 7 CNS. The 5-year local failure-free survival was 86%. Age, histology, and time to RT did not influence the risk of local failure. The 5-year regional failure-free survival was 92%: 100% for embryonal and 74% for alveolar (P=.03). However, there were no lymph node failures in patients with alveolar histology who were given PNI. The 5-year CNS failure-free survival was 83%: 100% without and 70% with ICE (P=.01); 95% without and 69% with cranial neuropathy (P=.02). The estimated 5-year event-free survival and overall survival were 61% for group III and 58% for group IV patients. CONCLUSIONS Distant failure was the most common type of failure among group IV patients. Patients with alveolar histology seem to benefit from PNI. The presence of ICE or cranial neuropathy portends a high risk of CNS failure, the most common pattern of failure among non-group IV patients. These patients may benefit from the addition of novel CNS-directed therapy.

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

PURPOSE To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). PATIENTS AND METHODS A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. RESULTS With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged ≤7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. CONCLUSIONS DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

Clear cell sarcoma of the gastrointestinal tract after very low-dose therapeutic radiation therapy: a case report

Childhood cancer survivors are at risk for developing second malignant neoplasms. Very-low-dose therapeutic radiation therapy (RT) may be used to treat infants with Stage 4S neuroblastoma. We report a case of a patient who subsequently developed clear cell sarcoma of the gastrointestinal tract nearly 15 years after treatment with very low-dose therapeutic RT (4.5 Gy) for Stage 4S neuroblastoma.

Barriers to conceiving sibling donors for sickle cell disease: perspectives from patients and parents

Objectives. The lack of matched sibling donors poses a significant barrier to utilizing hematopoietic cell transplantation (HCT), the only proven cure for children with sickle cell disease (SCD). Little is known about current patient and parent perspectives towards HCT for SCD. This study examines the perceived barriers of transplant, and the use of in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD), when there is no pre-existing sibling donor. Design. Semi-structured interviews were conducted with adult patients with SCD and parents of children with SCD in an urban medical center in the US. Transcribed data was analyzed using qualitative methods. Results. Of 23 participants, 17 reported having heard of HCT for SCD. Fewer knew of IVF or PGD as a means for conceiving an unaffected child (n =7) or to select a potential umbilical cord blood donor (n =1). The financial cost of IVF and PGD was perceived as a significant initial barrier to accessing these technologies, with the clinical risks of HCT and the ethical appropriateness of using PGD also identified as barriers. The value of informing families of these options was a recurring theme, even among respondents who personally disagreed with their application. Conclusion. The low utilization of curative strategies for SCD appears to be partly attributable to a lack of information about the technologies available to facilitate transplantation. Ethical reservations, while present, were not static and did not preclude patients’ and parents’ desire to be informed. We discuss the implications of these perceived barriers to the dissemination of advanced medical technologies for SCD.

Intensity-modulated radiation therapy with dose-painting for pediatric sarcomas with pulmonary metastases.

We examined patterns of failure in pediatric patients with thoracic sarcoma and pulmonary metastases treated with intensity‐modulated radiation therapy with dose‐painting (DP‐IMRT).

Phantosmia During Radiation Therapy A Report of 2 Cases

Phantosmia is an infrequently reported and poorly understood qualitative olfactory disorder characterized by the perception of a frequently unpleasant odor in the absence of an odorant stimulus. Peripheral phantosmia is hypothesized to involve abnormally active olfactory receptor neurons while central phantosmia is theorized to be the result of hyperactive neurons in the cortex. The authors present a case report that describes 2 patients with incomparable tumors and radiation fields who both experienced phantosmia featuring a halitosis-like odor during their courses of radiation therapy. Both the 6-year-old with diffuse intrinsic pontine glioma and the 15-year-old with World Health Organization grade II-III astrocytoma in the bifrontal lobes experienced significant distress and decreased quality of life during treatment because of the phantosmia, which resolved after completion of radiation therapy. To the best of the authors’ knowledge, these are the first descriptions of phantosmia during focal or whole-brain radiation therapy.

Intensity-Modulated Radiation Therapy With Dose Painting: A Brain-Sparing Technique for Intracranial Germ Cell Tumors.

We sought to assess patterns of failure in pediatric patients with intracranial germ cell tumors (GCT) treated with intensity‐modulated radiation therapy with dose painting (DP‐IMRT).

A PILOT STUDY OF BRENTUXIMAB VEDOTIN AND AVD CHEMOTHERAPY FOLLOWED BY 20 GY INVOLVED-SITE RADIOTHERAPY IN EARLY STAGE, UNFAVORABLE RISK HODGKIN LYMPHOMA

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hematology, Policlinico di Bari, Bari, Italy; Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy; Hematology‐Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione Pascale, IRCCS, Naples, Italy; Hematology, Ospedale G. Panico, Lecce, Italy; Hematology, Azienda Sanitaria Universitaria Integrata, Udine, Italy; Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Padova, Italy; Hematology, IRCCS Policlinico San Matteo, Pavia, Italy; Hematology, San Bortolo Hospital, Vicenza, Italy; Division of Medical Oncology A, National Cancer Institute, Aviano, Italy; Division of Hematology 1, IRCCS A.O.U. San Martino IST, Genoa, Italy

Teaching NeuroImages: Lymphomatoid granulomatosis involving lung and brain in an immunocompetent woman

A 56-year-old woman presented with 5 months of dysarthria and progressive gait changes. Examination revealed scanning speech, wide-based ataxic gait, and dysmetria. MRI demonstrated T2 abnormality with patchy enhancement within bilateral cerebellar hemispheres and supratentorial deep white matter (figure 1). Miliary lung lesions were present. Histopathologic examination of lung and cerebellum revealed lymphoproliferation. A third biopsy of FDG-PET avid …