Vascular events from carotid artery atherosclerosis after radiation therapy for laryngeal and hypopharyngeal cancer: the incidence and risk factors.

In this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60-74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3-78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction.

Deletion of caveolin scaffolding domain alters cancer cell migration.

Caveolin-1 (Cav-1) is an integral membrane protein that plays an important role in proliferative and terminally differentiated cells. As a structural component of Caveolae, Cav-1 interacts with signaling molecules via a caveolin scaffolding domain (CSD) regulating cell signaling. Recent reports have shown that Cav-1 is a negative regulator in tumor metastasis. Therefore, we hypothesize that Cav-1 inhibits cell migration through its CSD. HeLa cells were engineered to overexpress Cav-1 (Cav-1 OE), Cav-1 without a functional CSD (∆CSD), or enhanced green fluorescent protein (EGFP) as a control. HeLa cell migration was suppressed in Cav-1 OE cells while ∆CSD showed increased migration, which corresponded to a decrease in the tight junction protein, zonula occludens (ZO-1). The migration phenotype was confirmed in multiple cancer cell lines. Phosphorylated STAT-3 was decreased in Cav-1 OE cells compared to control and ∆CSD cells; reducing STAT-3 expression alone decreased cell migration. ∆CSD blunted HeLa proliferation by increasing the number of cells in the G2/M phase of the cell cycle. Overexpressing the CSD peptide alone suppressed HeLa cell migration and inhibited pSTAT3. These findings suggest that Cav-1 CSD may be critical in controlling the dynamic phenotype of cancer cells by facilitating the interaction of specific signal transduction pathways, regulating STAT3 and participating in a G2/M checkpoint. Modulating the CSD and targeting specific proteins may offer potential new therapies in the treatment of cancer metastasis.

Radiotherapy for locally recurrent rectal cancer treated with surgery alone as the initial treatment.

PURPOSE: Although the technical developments of radiotherapy have been remarkable, there are currently few reports on the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as initial treatment in this three-dimensional conformal radiotherapy era. Thus, we retrospectively evaluated the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as the initial treatment. MATERIALS AND METHODS: Thirty-two patients who underwent radiotherapy were enrolled in this study. The dose per fraction was 2.0-3.5 Gy. Because the treatment schedule was variable, the biological effective dose (BED) was calculated. RESULTS: Local control (LC) and overall survival (OS) rates from the completion of radiotherapy were calculated. The 1-, 2-, 3-, 4-, and 5-year LC rates were 51.5%, 24.5%, 19.6%, 19.6%, and 13.1%, respectively. LC rates were significantly higher for the high BED group (≥75 Gy10) than for the lower BED group (<75 Gy10). All patients who reported pain achieved pain relief. The duration of pain relief was significantly higher for the high BED group than for the lower BED group. The 1-, 2-, 3-, 4-, and 5-year OS rates were 82.6%, 56.5%, 45.2%, 38.7%, and 23.2%, respectively. There was a trend toward higher OS rates in with higher BED group compared to lower BED group. CONCLUSION: For patients with unresectable locally recurrent rectal cancer treated with surgery alone, radiotherapy is effective treatment. The prescribed BED should be more than 75 Gy10, if the dose to the organ at risk is within acceptable levels.

Usefulness of the dual energy field-in-field technique in breast tangential radiotherapy.

PURPOSE: In the field-in-field (FIF) technique in breast tangential radiotherapy, the energy of the subfield is usually the same as the energy of the main field. However, some studies have applied 10-18 MV to subfields in patients with large breasts. We compared two FIF plans in 66 breast cancer patients: in one, the energy of the subfield was the same as that of the main field (the mono energy plan); in the other, it was higher (the dual energy plan). MATERIALS AND METHODS: The photon energy of the subfield was 6 MV in the mono energy plan and 10 MV in the dual energy plan. The percentage of the planning target volume (PTV) receiving at least 105, 100, and 95% of the prescribed dose (V105, V100, and V95, respectively) was calculated, as were the maximum and mean doses delivered to the PTV (Dmax and Dmean, respectively). Clinical target volumes (CTVs) and the thickness of the breast between the chest wall and skin surface at the level of the nipple were measured. RESULTS: V95% was significantly higher in the dual energy plan than in the mono energy plan in patients with CTVs or breast thickness in the highest quartile. There were no significant differences in the other parameters of the two plans in these patients. CONCLUSION: These findings demonstrate the usefulness of the dual energy FIF technique in patients with large breasts receiving breast tangential radiotherapy.

Clinical outcomes of single or oligo-fractionated stereotactic radiotherapy for head and neck tumors using micromultileaf collimator-based dynamic conformal arcs.

PURPOSE: To assess the clinical outcomes of single or oligo-fractionated stereotactic radiotherapy (SRT) using dynamic conformal arcs (DCA) for head and neck tumors (HNTs). METHODS: Thirty-four consecutive patients with 35 lesions treated between 2005 and 2009 were retrospectively evaluated, of whom 85.7 % had recurrent or metastatic disease, and 45.7 and 34.3 % had previous radiotherapy and surgery, respectively. The median SRT dose was 22.3 Gy (11.2-32.8) in 2-4 fractions with a median interval of 7 days and 10.4 Gy (9.2-12.4) in one fraction. SRT was combined with upfront conventionally fractionated RT in 48.6 % of patients. RESULTS: The median follow-up periods were 18.4 months (2-84.1) for the entire cohort and 49.6 months for the survivors. The 1- and 2-year local control (LC) rates were 84.3 and 70.5 %, with the 1- and 2-year overall survival (OS) rates of 78.6 and 51.6 %. LC was significantly better for tumor volumes <25.6 cm(3) (p = 0.001). OS was significantly longer in patients without any disease outside the SRT site (p < 0.001), whereas LC after the SRT did not affect the OS. Late adverse events occurred in 9 patients, including cranial nerve (CN) injury (grade 3/4) in 2, brain radionecrosis in 5 (grade 1), and fatal bleeding in 2 patients harboring uncontrolled lesions abutting the carotid artery. CONCLUSIONS: DCA-based SRT can confer relatively long-term LC with acceptable toxicity in selected patients with HNTs. The patients with CN involvement or tumor volume ≥25.6 cm(3) were deemed unsuitable for this treatment regimen.