Outcome of limited-stage nodular lymphocyte-predominant Hodgkin lymphoma and the impact of a PET-adapted approach.

Radiotherapy (RT) is typically incorporated into the treatment of limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), although it remains unknown whether chemotherapy alone may be suitable in select patients. We evaluated outcomes of limited-stage NLPHL at BC Cancer on the basis of era-specific guidelines: routine RT era, 1995 to 2005 (n = 36), combined modality with 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by RT or RT alone; positron emission tomography (PET) era, after 2005 (n = 63), ABVD alone (4 cycles) if the PET scan after the second cycle of ABVD (PET2) is negative, or treatment is changed to RT if PET2 is positive. Median age of patients was 38 years (range, 16-82 years), 73% were male, and 43% had stage II. With a median follow-up of 10.5 years for all patients, 5-year progression-free survival (PFS) was 91% [corrected] and was 97% for overall survival (OS), with no difference by treatment era (PFS, P = .15; [corrected] OS, P = .35). For the 49 patients who had a PET2 scan, 86% were PET negative and 14% were PET positive by Deauville criteria with 5-year PFS rates of 92% and 80% (P = .87) [corrected], respectively. This is the largest study of a PET-adapted approach in NLPHL and supports that ABVD alone may be a viable option in select patients with a negative PET2 scan, with consideration of acute and long-term toxicities.

Therapeutic Implication of Genomic Landscape of Adult Metastatic Sarcoma.

PURPOSE: This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options. METHODS: Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing. RESULTS: The most frequent genomic alterations in this cohort are large-scale structural variation and somatic copy number variation. Outlier RNA expression as well as somatic copy number variations, structural variations, and small mutations together suggest the presence of one or more potential therapeutic targets in the majority of patients in our cohort. Point mutations or deletions in known targetable cancer genes are rare; for example, tuberous sclerosis complex 2 provides a rationale for targeting the mammalian target of rapamycin pathway, resulting in a few patients with exceptional clinical benefit from everolimus. In addition, we observed recurrent 17p11-12 amplifications, which seem to be a sarcoma-specific event. This may suggest that this region harbors an oncogene(s) that is significant for sarcoma tumorigenesis. Furthermore, some sarcoma tumors carrying a distinct mutational signature suggestive of homologous recombination deficiency seem to demonstrate sensitivity to double-strand DNA-damaging agents. CONCLUSION: Integrated large-scale genomic analysis may provide insights into potential therapeutic targets as well as novel biologic features of metastatic sarcomas that could fuel future experimental and clinical research and help design biomarker-driven basket clinical trials for novel therapeutic strategies.

Acute Inflammatory Response During Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer: A Case Report.

We report on a 56-year-old Caucasian female, diagnosed with locally advanced, hormone-receptor-positive, and human epidermal growth factor receptor 2 (HER2)-positive cancer of the left breast. The patient received neoadjuvant chemotherapy with adriamycin/cyclophosphamide (AC) followed by docetaxel/trastuzumab. A partial clinical and radiographical response was documented after four cycles of AC. Approximately one week after the first cycle of docetaxel and trastuzumab, the patient presented with diffuse edema, erythema, and induration involving the entire left breast. The differential diagnoses included infection, inflammatory response/reaction to docetaxel, or cancer progression. After a multidisciplinary review, the decision was made to stop the docetaxel and deliver neoadjuvant radiation treatment concurrent with trastuzumab. Approximately four weeks after radiation therapy completion, the patient underwent a left total mastectomy and axillary dissection, with pathologic complete response (pCR) in the breast and axillary nodal disease. After surgery, systemic therapy was resumed with paclitaxel and trastuzumab, with a plan to start adjuvant endocrine therapy after completion of chemotherapy. We will discuss clinical considerations in the management of the unexpected findings of acute inflammatory response in the breast and nodal regions during neoadjuvant chemotherapy. Associations between intrinsic breast cancer subtype and pCR in locally advanced breast cancer will also be reviewed.

Radiation generates an abscopal response and complete resolution of metastatic squamous cell carcinoma of the anal canal: a case report.

The abscopal effect is a rare phenomenon in the setting of radiation therapy (RT) for metastatic cancer where tumor regression occurs distant from the site of treatment. A proposed mechanism of the abscopal effect is the activation of a systemic antitumor immune response by localized RT. We report the first case, to our knowledge, of the abscopal effect in squamous carcinoma of the anal canal with metastases to pelvic lymph nodes, liver and bone. After palliative RT to the pelvis with sensitizing chemotherapy, complete response was observed not only in the primary tumor but also in bone and multiple liver metastases at 4 months after treatment, an effect that remained durable at 4-year follow-up. Understanding of the abscopal effect and the immune mechanisms associated with anal cancer may lead to new avenues of research to improve outcome for patients with this rare disease.

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion-positive lung cancer patient.

Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene-addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)-positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.