ABSTRACT
Among various altered fractionation schedules, only hyper-fractionation has proven increased local control in head and neck cancers. MARCH (Metanalyses of Hyperfractionated or Accelerated radiotherapy in Head and neck cancer) concluded that hyper-fractionated radiotherapy in head and cancers had a survival benefit. This study attempts to combine the benefits of hyper-fractionation with the tissue sparing qualities of intensity modulated radiotherapy. Three patients with advanced oro-pharyngeal cancers were treated with HF-IMRT (Hyperfractionated-IMRT) (2 oropharynx, 1 hypopharynx). Two phase treatment planning with phase I prescribed to high risk volume (HRV) and intermediate risk volume (IRV), 60Gy in 50 fractions at 1.2Gy per fraction, 2 fractions/day, 6-8 h apart. The low risk volume (LRV) received 55Gy to the 95% volume at 1.1Gy per fraction in the same 50 fractions. In phase II, HRV alone was prescribed 1960cGy in 20 fractions over two weeks. Total dose to HRV was 7960cGy in 7 wk. No concurrent chemotherapy was given. Treatment was completed as planned (<60 days; break of 11 days was due to radiation toxicity). Only one patient had grade III toxicity. All three required diet modifications, an average weight loss of 3 kg and no hospitalization required during treatment. This pilot study shows the feasibility of an effective hyper-fractionation with IMRT for head and neck cancers. A Phase II trial is required to prove its efficacy.
ABSTRACT
Glioblastoma Multiforme (GBM) is a high-grade brain tumour with the most dismal prognosis. There are very few reports on second malignancies occurring in GBM patients, as the survival has been short. Second malignancies have been reported after treatment of malignancies with radiation therapy and chemotherapy especially after 5 to 10 y of treatment. Here in, we present a very unique case where a patient succumbed to sinonasal carcinoma occurring one and half years after treatment of GBM. A 17-year-old boy was diagnosed to have GBM and underwent surgery followed by chemoradiation and adjuvant chemotherapy with Temozolamide. He presented with undifferentiated sinonasal carcinoma, in the sinonasal region outside the radiation field within two years of treatment. Here we discuss the histology and possible chances of it being a second malignancy.
ABSTRACT
PURPOSE: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. EXPERIMENTAL DESIGN: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. RESULTS: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. CONCLUSIONS: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Adult , Aged , Breast Neoplasms/surgery , Class I Phosphatidylinositol 3-Kinases , DNA Mutational Analysis/methods , DNA, Neoplasm/chemistry , Exons/genetics , Female , Humans , Middle Aged , Mutation , Neoplasm Staging , Phosphatidylinositol 3-Kinases/genetics , Polymerase Chain Reaction/methods , Postoperative Period , Preoperative Period , Prospective Studies , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Digital polymerase chain reaction is a new technology that enables detection and quantification of cancer DNA molecules from peripheral blood. Using this technique, we identified mutant PIK3CA DNA in circulating ptDNA (plasma tumor DNA) from a patient with concurrent early stage breast cancer and non-small cell lung cancer. The patient underwent successful resection of both her breast and lung cancers, and using standard Sanger sequencing the breast cancer was shown to harbor the identical PIK3CA mutation identified in peripheral blood. This case report highlights potential applications and concerns that can arise with the use of ptDNA in clinical oncology practice.
