Positron imaging for verification of irradiation field during radiotherapy.

AIM OF STUDY: The present study was designed to investigate the application of positron images from photonuclear reactions to verify the location of targeted radiation in vivo. MATERIALS AND METHODS: The phantom study was conducted with distilled water, porcine muscle, porcine adipose tissue, and graphite; these subjects were irradiated separately with 50 MV photons generated by an MM50 Racetrack Microtron. The positron emission activity was measured using a Geiger counter, and the radioactive decay curves for each of the irradiated materials were then established. The positron emission tomography (PET) images of the three tissue models were also achieved using the same radiation conditions. The in vivo PET imaging study was also conducted in tumor-bearing rabbits. RESULTS: Our results demonstrated that the PET imaging could be used to verify the position of the irradiation field in vivo. The dose distribution images of photonuclear reactions of 11 C and 15 O were uniform, using 2-Gy 50 MV photons. CONCLUSIONS: The factors influencing the half-life of radiation activity in various tissues were different from the first order kinetic reaction in physics.

Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma.

Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.

[Effect of "Xinjingjie mouthrinse" on prevention and treatment of radiation-induced oral mucositis].

PURPOSE: To investigate the effect of "Xinjingjie compound lysostaphin antibacterial collutorium" on prevention and treatment of radiation-induced oral mucositis in a prospective, randomized and double-blind clinical trial. METHODS: Sixty patients with oral cancer to be treated with radiotherapy were randomized into the experimental and control group. The experimental group (30 patients) was treated with "Xinjingjie mouthrinse" during the full course of radiotherapy, 4 times daily with 5 mL and 5 min each time. The control group (30 patients) rinsed the mouth in the same way with normal saline. Oral mucositis was assessed according to the RTOG criteria. The severity of mucositis and the degree of pain were recorded and photographed. Patients shouldn't be treated with other drugs until the level of oral mucositis reached above grade III. The results were statistically analyzed using Stata 12.0 software packages. RESULTS: Age, gender, radiotherapy techniques and dose showed no significant difference between the 2 groups (P>0.05). The first onset of oral mucositis in the experimental group was later than that in the control group (11.0 times:9.1 times,P<0.05), and the incidence of pain at the early time of radiotherapy was lower (36.7%: 70.0%, P<0.05). Also, the onset time of grade III oral mucositis in the emperimental group was later than that in the control group (18.9 times:15.9 times,P<0.05), and the incidence of grade III oral mucositis in the experimental group was lower (63.3% vs. 90.0%, P<0.05). CONCLUSIONS: "Xinjingjie mouthrinse" is worthwhile to be used in clinic because it can delay the occurrence time of radiation-induced oral mucositis, alleviate pain and reduce the indication of grade III oral mucositis.

Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma.

BACKGROUND: We compared outcomes and xerostomia grade after postoperative intensity-modulated radiation therapy (IMRT) and conventional radiotherapy (RT) in patients with oral and oropharyngeal carcinoma. METHODS: Eighty-eight patients with oral cavity (n = 77) and oropharyngeal (n = 11) carcinoma underwent postoperative IMRT (n = 44) or conventional RT (n = 44). Outcomes, failure patterns, volume, doses, salivary gland V30, and xerostomia grade were evaluated. The median follow-up was 53 months (range, 48-58 months). The median interval from surgery to RT was 4 weeks (range, 3-6 weeks). RESULTS: Twenty-one patients (7 and 14 for the IMRT and conventional RT groups, respectively) experienced local-regional failure. For the IMRT group, all 7 local-regional failures occurred in the high-dose target volumes. For the conventional RT group, there were 12 in-field failures, 1 at the margin, and 1 out-of-field. Nine patients experienced distant failure (5 and 4 for the IMRT and conventional RT groups, respectively). The 4-year local-regional control, disease-free survival (DFS), overall survival (OS), and distant-metastasis rates for the IMRT and conventional RT groups were 84.1% versus 68.2% (p = .055), 68.2% versus 52.3% (p = .091), 70.5% versus 56.8% (p = .124), and 11.4% versus 9.1% (p = .927), respectively. Xerostomia grade after RT was lower for IMRT compared to conventional RT (p < .001). CONCLUSION: Postoperative IMRT for oral and oropharyngeal carcinoma significantly improves mean dose, salivary gland V30, and xerostomia grade when compared to conventional RT. The predominant failure pattern was local. No differences were found in survival outcomes between both groups. There was a marginal difference in local-regional control.

Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma.

PURPOSE: To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety. RESULTS: Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control. CONCLUSION: Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.

Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy: a randomized study.

OBJECTIVES/HYPOTHESIS: Is the severity of acute oral mucositis in patients who receive postoperative intensity-modulated radiotherapy (PO-IMRT) for oral tongue squamous cell carcinoma (SCC) reduced by sparing the oral mucosa outside of the planning target volume (PTV)? STUDY DESIGN: Prospective, randomized trial. METHODS: Forty-eight patients with oral tongue SCC who received PO-IMRT at our institution were randomized to two groups: the oral-sparing (OR-SP) group and oral-unsparing (OR-USP) group. For the OR-SP group (n = 24), the oral mucosa outside of the PTV was spared. Furthermore, the mucosa including the bilateral cheeks, upper lip, and lower lip was defined as the united site and given <32 Gy. For the OR-USP group (n = 24), none of the oral mucosa was protected. The severity of clinical acute mucositis in each patient was assessed weekly during PO-IMRT until completely healed. Oral mucositis was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Dosimetry and therapeutic measures related to acute mucositis between the two groups were compared. RESULTS: During PO-IMRT, no patient experienced grade 4+ acute mucositis in any oral site. Compared to the OR-USP group, there was less grade 2 and 3 mucositis in the united site of the OR-SP group (0% and 25% vs. 45.8% and 54.2%, respectively; P = .000). Also, the mean dose to the united site was significantly lower with OR-SP compared to OR-USP (41.8 ± 7.4 Gy vs. 58.8 ± 2.2 Gy; P = .000). The OR-SP group was associated with significant reductions in the use of analgesics (P = .043) and intravenous antibiotics (P = .039). No recurrences were detected in the vicinity of the spared oral mucosa (the united site) during a median follow-up time of 30 months. CONCLUSIONS: OR-SP PO-IMRT for patients with oral tongue SCC resulted in a significant decrease in the severity of acute mucositis and improved quality of life. The sparing of the oral mucosa outside of the PTV is safe and does not compromise oncologic outcomes.

Impact of salivary gland dosimetry on post-IMRT recovery of saliva output and xerostomia grade for head-and-neck cancer patients treated with or without contralateral submandibular gland sparing: a longitudinal study.

PURPOSE: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. METHODS AND MATERIALS: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n=5 patients) and postoperative (n=47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). RESULTS: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. CONCLUSIONS: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.