Background and Purpose: To assess whether the pretreatment FDG-PET defined biologic target volume (PET-BTV) correlates with the anatomical sites of loco-regional failure (LRF) after RT for head & neck cancer (HNC).

The 5-year survival rate for patients with stage III non-small cell lung cancer (NSCLC) is 10%. A number of genetic alterations are associated with this disease including mutations and amplifications of EGFR (70%) and Ras (20-30%), both of which are upstream of PI3K. Our previous data show that these regulate tumor radiation sensitivity. Here we ask whether the activation of this pathway has prognostic relevance in NSCLC. Two series of patients were retrospectively analyzed. The first series consisted of 23 Stage III NSCLC patients treated preoperatively with a chemo/radiation protocol. The second consisted of 12 Stage III NSCLC patients treated with chemo/ radiation without surgery who had survived more than 2 years. Expression levels of EGFR and Her-2 were assessed by immunohistochemical staining. PI3K signaling was evaluated by staining for phosphorylated Akt (P-Akt), a downstream target of PI3K. The staining for EGFR, Her-2, and P-Akt were related to outcome in the two groups. Additionally, the importance of PI3K signaling was evaluated in 3 NSCLC cell lines using a pharmacological blockade of PI3K by LY294002. In the first series of patients, 43% were positive for EGFR, 5% for Her-2, and 82.6% for P-Akt. Of the survivors, 25% were positive for EGFR, 0% for Her-2, and 42% for P-Akt. For P-Akt, this difference had a probability calculation of 0.003. The three NSCLC cell lines that we tested were found to have high levels of P-Akt. Pharmacologically inhibiting PI3K led to decreased Akt phosphorylation and radio sensitization of all three cell lines. The finding that NSCLC survivors treated by radiation have lower levels of PI3K and Akt signaling is consistent with the idea that inhibition of Akt leads to radio sensitization. This further suggests that Akt might be a useful target for sensitization of NSCLC to radiation.

No abstract

The toxicity of radiation to living tissues was discovered soon after the discovery of radioactivity itself and this toxicity is the basis for cancer therapy with radiation. Although this mode of therapy is often effective, its success is far from assured. One major difficulty in the implementation of radiotherapy is that normal tissues are also sensitive to killing by radiation so that treatment is often limited by the tolerance of normal tissues for radiation. Thus methods that sensitize tumor cells while sparing normal tissues could potentially lead to greater success with radiation as a therapy. Oncogenes are frequently altered in tumors, but are not in normal tissue making them potential targets for altering radiosensitivity and apoptosis in tumors.

No abstract

Despite modern chemotherapy and RT, patients with limited-stage EPSCC do poorly. Consistent with previous findings the majority of the first failures are distant. Brain failures in this series were uncommon despite no prophylactic cranial radiation. These findings support the need for further studies in an attempt to improve systemic therapies for this disease.

Purpose-To determine if concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes.Methods & Materials-A total of 630 post prostatectomy patients were retrospectively identified that were treated with 3-D conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical Failure (BF) was defined as PSA ≥ 0.2 ng/mL above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of: BF, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression or distant failure. Multivariable-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS.Results-Low, intermediate, and high risk patients made up 10%, 24%, and 66% of patients, respectively. Mean RT dose was 68Gy. Twenty-four percent of patients received concurrent ADT (HRT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-yr PFS was 4.0 yrs for HRT vs. 3.4 yrs for non-HRT patients (p=0.22). Multivariable analysis demonstrated that concurrent ADT (p=0.05), Gleason score (p<0.001), and pre-RT PSA (p=0.03) were independent predictors of PFS. When stratified by risk group, the benefits of ADT (HR = 0.65, p=0.046) was significant only for high risk patients.Conclusions-This retrospective study has demonstrated a PFS benefits of concurrent ADT during salvage prostate RT. This benefit was observed only in high risk patients.

Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop platinum-resistant disease with poor prognosis. Although reports suggest that integrin-linked kinase (ILK) is a potential target for ovarian cancer treatment, identification of ILK downstream effectors has not been fully explored. The purpose of this study was to investigate the molecular and biological effects of targeting ILK in cisplatin-resistant ovarian cancer. Western blot analysis showed that phosphorylation levels of ILK were higher in cisplatin-resistant compared with cisplatin-sensitive ovarian cancer cells. Further immunohistochemical analysis of ovarian cancer patient samples showed a significant increase in phosphorylated ILK levels in the tumor tissue when compared to normal ovarian epithelium. Targeting ILK by small-interfering RNA (siRNA) treatment reduced cisplatin-resistant cell growth and invasion ability, and increased apoptosis. Differential gene expression analysis by RNA sequencing (RNA-Seq) upon ILK-siRNA transfection followed by Ingenuity Pathway Analysis (IPA) and survival analysis using the Kaplan–Meier plotter database identified multiple target genes involved in cell growth, apoptosis, invasion, and metastasis, including several non-coding RNAs. Taken together, results from this study support ILK as an attractive target for ovarian cancer and provide potential ILK downstream effectors with prognostic and therapeutic value.