[Extranodal NK/T cell lymphoma, nasal type with local recurrence in the contralateral nasal cavity 15 years after initial sequential chemoradiotherapy].

A 72-year-old woman was diagnosed with extranodal NK/T cell lymphoma of the right nasal cavity and received sequential radiochemotherapy comprising focal radiotherapy and THP-COP chemotherapy. Showed a complete tumor response to the treatment; however, the tumor recurred in the contralateral right nasal cavity 15 years after the initial treatment. This was judged to be a marginal recurrence in the radiation field. After four cycles of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy, a second complete response was achieved. It is possible that another recurrence occurs in the future, and if the lesion is localized at the time of recurrence, it may be possible to control the disease again. Careful follow-up is considered necessary.

Pharmacokinetics of initial full and subsequent reduced doses of S-1 in patients with locally advanced head and neck cancer-effect of renal insufficiency.

BACKGROUND: S-1 is a combination of tegafur [metabolized to 5-fluorouracil (5-FU)] with the modulators gimeracil (5-chloro-2,4-dihydroxypyridine) and oteracil potassium. 5-Chloro-2,4-dihydroxypyridine maintains plasma 5-FU concentrations by inhibiting dihydropyrimidine dehydrogenase, a pyrimidine catabolism enzyme that degrades 5-FU. As 50% of 5-chloro-2,4-dihydroxypyridine is excreted in urine, renal insufficiency may increase its blood level, increasing 5-FU concentrations. We investigated whether special dose modification is needed in the presence of renal insufficiency. OBJECTIVE: We compared steady state pharmacokinetics of 5-FU for the initial S-1 dose and reduced doses in patients with head and neck cancer requiring dose reduction due to renal and non-renal toxicities. METHODS: Chemoradiotherapy with S-1 and cisplatin was administered every 5 weeks for two courses with a radiation dose totaling 70 Gy over 33-35 fractions. Two additional courses of adjuvant chemotherapy were administered in the case of an objective response. The S-1 and/or cisplatin dose was reduced in response to renal, hematologic or other toxicities. The primary endpoint was the change in area under the plasma concentration-versus-time curve from time 0-10 hours (5-FU AUCss 0-10) between the initial and reduced S-1 doses. RESULTS: Although the mean 5-FU levels in patients with non-renal toxicities significantly decreased between the full and reduced dose, the full-dose and reduced-dose mean maximum 5-FU plasma concentrations at steady state (Css max) and AUCss 0-10 in patients with renal insufficiency were similar. CONCLUSIONS: Standard S-1 dose reduction for renal toxicity did not result in a significant decrease in 5-FU levels at steady state. A greater reduction to lower plasma 5-chloro-2,4-dihydroxypyridine may be necessary in patients with renal insufficiency.

Impact of prophylactic percutaneous endoscopic gastrostomy tube placement on treatment tolerance in head and neck cancer patients treated with cetuximab plus radiation.

OBJECTIVE: We conducted a retrospective analysis to evaluate the efficacy and safety of cetuximab plus radiation with or without prophylactic percutaneous endoscopic gastrectomy in locally advanced squamous cell carcinoma of the head and neck patients who were not suitable to receive platinum. PATIENTS AND METHODS: We reviewed the case records of 27 locally advanced squamous cell carcinoma of the head and neck patients treated with cetuximab plus radiation (RT) between January 2013 and July 2014. No patient was able to receive platinum because of renal dysfunction or other contraindications. Patients received an initial dose of cetuximab of 400 mg/m(2), followed by weekly doses of 250 mg/m(2). The total dose of radiotherapy was 66-70 Gy in five daily fractions of 2-2.12 Gy per week. RESULTS: The incidence of leukopenia was significantly higher in patients without percutaneous endoscopic gastrectomy placement than in those with (67.5% vs. 7%, P = 0.002). The incidence of Grade 3 or 4 mucositis tended to be higher in patients without percutaneous endoscopic gastrectomy placement than in those with (83% vs. 47%, P = 0.058). Five of twelve patients without percutaneous endoscopic gastrectomy placement required interruption of treatment. More patients without percutaneous endoscopic gastrectomy placement had significantly >10% weight loss than patients with (75% vs. 27%, P = 0.013). The overall response rate was 56% in all patients. The 1-year progression-free survival rate was 30.6% in all patients. CONCLUSIONS: Prophylactic percutaneous endoscopic gastrectomy-feeding tube placement could reduce the incidence of severe toxicities, including mucositis and weight loss, and avoid RT interruption. These results require confirmation in a larger study.

Patterns of failure after postoperative intensity-modulated radiotherapy for locally advanced and recurrent head and neck cancer.

OBJECTIVE: To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy. METHODS: A retrospective chart review was performed. RESULTS: Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25-115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of <5%, except for mucositis. No severe toxicities associated with the flap reconstruction were observed either. CONCLUSION: Postoperative intensity-modulated radiotherapy appears to be effective and feasible for patients with head and neck squamous cell carcinoma.

Incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases.

BACKGROUND: Adverse events associated with re-irradiation for painful bone metastases have not been adequately evaluated. The purpose of this study was to clarify the incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases. METHODS: Data for 61 consecutive patients who required re-irradiation for spine or pelvic bone metastases between April 2009 and March 2013 were retrospectively evaluated in this study. The adverse events, biologically effective dose (BED), and the responses to pain and/or symptoms caused by cord compression were evaluated. RESULTS: Of the 61 patients, 52 were included in the study and their data were analyzed. The site of re-irradiation was the spine in 35 patients (67 %), and the pelvic bone in the remaining 17 patients (33 %). The median follow-up period was 170 days (range 5-1,644 days) for all eligible patients. The median interval from initial radiation therapy to re-irradiation was 161 days (range 26-2,909 days). The median cumulative BED from the initial radiation and re-irradiation was 115 Gy (range 80-155 Gy2). The acute adverse events were all below grade 2 in severity, except for two patients who showed grade 3 pain flare within a few days after the start of re-irradiation. No late adverse events were observed in this study that were grade 3 or of worse severity. CONCLUSIONS: The incidence and severity of adverse events after re-irradiation for spine or pelvic bone metastases were within acceptable limits in this study.

DeCoP, a Dermatitis Control Program using a moderately absorbent surgical pad for head and neck cancer patients receiving radiotherapy: a retrospective analysis.

OBJECTIVE: We evaluated the clinical characteristics of a Dermatitis Control Program based on a moderately absorbent surgical pad for head and neck cancer patients undergoing (chemo)radiotherapy. METHODS: We retrospectively reviewed patients who underwent definitive radiotherapy or post-operative radiotherapy and were treated during radiotherapy with a Dermatitis Control Program using a moderately absorbent surgical pad from May 2011 through April 2012. The main protocol was the 'Dermatitis Control Program', a systematic program which consists of a three-step ladder. When radiation dermatitis reached Grade 2, the irradiated area was covered with a moderately absorbent surgical pad. All outpatients and their families were instructed on how to cover and moisten the irradiated area. Radiation dermatitis was evaluated by physicians or nurses at an outpatient clinic and reviewed from photographs. RESULTS: A total of 116 head and neck cancer patients were treated by definitive or adjuvant (chemo)radiotherapy in our hospital from May 2011 through April 2012. Of these, 85 patients managed their dermatitis using a new device and they were reviewed. Fifty-five patients received chemoradiotherapy, of whom 22 received induction chemotherapy before chemoradiotherapy. Median radiation dose at the onset of Grade 2 dermatitis was 60.0 Gy (range 40-71.2 Gy). Median time to recover from the end of radiotherapy was 10.5 days (range 0-25 days). The rate of recovery from Grade 2 dermatitis within 2 weeks after the end of radiotherapy was 89.4%. The rate of Grade 3 dermatitis was 7.1, with 6.7% in radiotherapy and 7.3% in chemoradiotherapy. CONCLUSIONS: This study suggests that the DeCoP protocol with a moderately absorbent surgical pad might be useful for the treatment of radiation dermatitis in clinical practice.

Late toxicity of proton beam therapy for patients with the nasal cavity, para-nasal sinuses, or involving the skull base malignancy: importance of long-term follow-up.

BACKGROUND: Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para-nasal sinuses, or involving the skull base. METHODS: Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0). RESULTS: From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4). CONCLUSIONS: In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary.

Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases.

BACKGROUND: Although the use of Sr-89 chloride in the treatment of patients with prostate and breast cancer has been widely reported, little information is available about its use for other malignancies. Here, we retrospectively analyzed the clinical profile of Sr-89 chloride in various patients with painful bone metastases. METHODS: Entry criteria were a pathologically proven malignancy, clinically diagnosed multiple bone metastases, and adequate organ function. Sr-89 chloride (Metastron) was given by single intravenous infusion at 2 MBq/kg over 2 min. Self-reported outcome measures were used as a response index, including pain diary data on a 0-10 numeric rating scale (NRS). RESULTS: Fifty-four consecutive patients with painful bone metastases were treated with Sr-89 chloride at the National Cancer Center Hospital East between March 2009 and July 2011, consisting of 26 with breast/prostate cancer and 28 with other malignancies (lung 8, head and neck 6, colorectal 6, others 8). Thirteen (24 %) patients experienced a transient increase in pain, which was categorized as a flare-up response. Grade 3-4 anemia was observed in 6 patients, 3 of whom required blood transfusion. Regarding efficacy, response rates and complete response rates were 71.2 % and 34.6 %, respectively, and time to response from the initiation of treatment was 36 days (range, 13-217). No significant difference in response rates was seen between patients with breast/prostate cancer and other cancers (breast/prostate 69.2 %, other 73.1 %; p = 0.76). CONCLUSIONS: As in patients with breast and prostate cancer, Sr-89 chloride is a promising agent for the treatment of painful bone metastases in patients with various other malignancies.

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

OBJECTIVE: The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. METHODS: Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. RESULTS: One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. CONCLUSIONS: Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

A Dermatitis Control Program (DeCoP) for head and neck cancer patients receiving radiotherapy: a prospective phase II study.

PURPOSE: We speculated that a systematic program to manage radiation dermatitis might decrease the incidence of severe or fatal cases in head and neck cancer patients receiving radiotherapy. Here, we conducted a prospective phase II study to clarify the clinical benefit of a Dermatitis Control Program (DeCoP) that did not use corticosteroids. PATIENTS AND METHODS: Head and neck cancer patients scheduled to receive definitive or postoperative radiotherapy were enrolled. Radiation dermatitis was managed with a DeCoP consisting of a three-step ladder: Step 1, gentle washing; Step 2, gentle washing and moistening of the wound-healing environment; Step 3, prevention against infection, gentle washing and moistening of the wound-healing environment. The primary endpoint was the incidence of grade 4 dermatitis. RESULTS: A total of 113 patients were registered between January 2009 and February 2010. Eighty patients received radiotherapy as an initial approach, while the remaining 33 received radiotherapy postoperatively. Grade 3 and 4 dermatitis events occurred in 11 (9.7%) and 0 (0%, 95% confidence interval 0-3.2%) patients, respectively. Median radiation dose at the onset of grade 2 dermatitis was 61.5 Gy (range 36-70 Gy) and median period between onset and recovery was 14 days (range 1-46 days). CONCLUSION: The Dermatitis Control Program has promising clinical potential. Radiation dermatitis might be manageable if gentle washing and moistening of the wound-healing environment is done.

The effectiveness of moisturizer on acute radiation-induced dermatitis in breast cancer patients: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to investigate the effectiveness of moisturizers on acute radiation dermatitis (ARD) in breast cancer patients receiving radiotherapy (RT). METHODS: PubMed, the Cochrane Library, CINAHL, and Ichushi-Web were searched for randomized controlled trials (RCTs) from April 2015 to March 2020. Assessments included type of intervention, cohort, outcomes, and quality of evidence. To evaluate the effect of moisturizer on ARD, we restricted analyses to studies comparing with standard skin care or no treatment. Outcomes were ARD severity and skin-related QOL (quality of life). Eligible studies were identified, and risk ratios and mean differences were extracted to compare outcome data. RESULTS: We screened 210 RCTs along with 14 studies included in a previous iteration of this analysis (2016), supplemented by a hand search (n = 9). Finally, we included 6 RCTs that investigated the effectiveness of standard type moisturizers in breast cancer patients receiving RT. Evidence (weak certainty) suggests that moisturizer use might reduce ≥ grade 3 ARD. QOL assessed by Skindex-16 improved with moisturizer use. Pain and pruritus measured by the visual analog scale (VAS) resulted in a smaller and nonsignificant difference in favor of moisturizer use. However, the certainty of the evidence was very weak in QOL. CONCLUSIONS: The proactive use of moisturizer may play a role in reducing ARD and improving skin-related QOL, although the certainty of the evidence was weak to very weak. Future high-quality RCTs should be initiated to strengthen these results.

Impact of Proton Beam Irradiation of an Anatomic Subsegment of the Liver for Hepatocellular Carcinoma.

PURPOSE: The objective of this research was to elucidate the impact on the prognosis, including the survival prognosis, resulting from proton beam irradiation of an anatomic subsegment of the liver (ASPT) for the treatment of hepatocellular carcinoma (HCC). METHODS AND MATERIALS: A total of 110 patients who received a diagnosis of HCC were analyzed in this retrospective study. Definitive proton beam therapy was delivered at a dose of 76 Gy (relative biological effectiveness) in 20 fractions between January 2008 and December 2015. When the HCC widely abutted blood vessels or when multiple HCC tumors occurred within the same liver subsegment, the clinical target volume was outlined as an anatomic subsegment of the liver, according to the portal territory, containing the tumor. In the remaining cases, the clinical target volume was delineated by adding a 5-mm margin around the gross tumor volume. The overall survival (OS), progression-free survival (PFS), and local control rates and adverse events were assessed. A review of the medical charts assessed adverse events that occurred during and after the treatment and were classified according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up duration was 36.5 months (range, 1-90.6 months). The median age of the patients was 73 years (range, 48-90 years). ASPT was performed in 31 patients (28%). Three-year OS, PFS, and local control rates were 74.2%, 40.4%, and 91.7%, respectively. Multivariate analysis identified ASPT as a factor that significantly improved PFS (P = .049) but not OS (P = .79). No association was found between ASPT and the frequency of grade ≥3 acute/late adverse events. CONCLUSIONS: ASPT was associated with a reduction in the rate of tumor progression and no significant toxicity but was not associated with OS.

Efficacy and safety of accelerated fractionated radiotherapy without elective nodal irradiation for T3N0 glottic cancer without vocal cord fixation.

BACKGROUND: The purpose of this study was to evaluate accelerated fractionated radiotherapy (AFRT) without elective nodal irradiation (ENI) for T3N0 glottic cancer (GC) without vocal cord fixation, especially in comparison with chemoradiotherapy (CRT) and hyperfractionated radiotherapy (HFRT) both of which included ENI. METHODS: The medical charts of patients with T3N0GC without cord fixation received definitive radiotherapy between June 2005 and March 2018 were reviewed. RESULTS: A total of 74 patients were analyzed. After a median follow-up time of 46 months (range, 12-141), 3-year local failure in AFRT/CRT/HFRT (n = 41/10/23) was 10%/20%/26%, 3-year regional failure 6%/0%/9%, 3-year progression-free survival 71%/69%/74%, and 3-year overall survival 77%/100%/87%. There were no significant differences among three groups in recurrence or survival. Grade 3 adverse events (AEs) were noted in 5/2/8 patients (12%/20%/35%) in AFRT/CRT/HFRT, respectively. There were no Grade 4/5 AEs. CONCLUSIONS: AFRT without ENI is an effective and feasible treatment for T3N0GC without cord fixation.

Swallowing disorder following salvage total pharyngo-laryngo-esophagectomy with free jejunum reconstruction.

For recurrent cases or residual cases following concomitant chemo-radiation therapy (CCRT), salvage surgery is a frequently used treatment options. A swallowing disorder is one of the major complications of CCRT. The purpose of the present study was to evaluate the effect of CCRT on swallowing function in patients who underwent salvage total pharyngo-laryngo-esophagectomy (TPLE), and to evaluate the importance of pharyngeal constriction in patients who underwent TPLE. Between 2008 January and 2014 May, 54 patients were treated with salvage TPLE following CCRT or TPLE at the National Cancer Center Hospital East, Chiba, Japan and were included in the present study. A total of 14 patients underwent salvage TPLE following CCRT for recurrence or residual tumor (the salvage TPLE group), and 40 patients underwent TPLE as initial treatment (the TPLE group). The pharyngeal constriction score and the post-swallowing oropharyngeal residue rate were evaluated, and inadequate velopharyngeal closure was assessed by videofluorography. The pharyngeal constriction score of the salvage TPLE group was poorer than that of the TPLE group (P<0.05). The bolus residue in the oropharynx was significantly larger in the salvage TPLE group than in the TPLE group (P<0.05). With regards to inadequate velopharyngeal closure, there was no significant difference between the TPLE group and the salvage TPLE group (P>0.99). The results of the present study indicate that the swallowing function of patients who undergo salvage TPLE may be affected by CCRT.

Proton-beam therapy for olfactory neuroblastoma.

PURPOSE: To analyze the feasibility and efficacy of proton-beam therapy (PBT) for olfactory neuroblastoma (ONB) as a definitive treatment, by reviewing our preliminary experience. Olfactory neuroblastoma is a rare disease, and a standard treatment strategy has not been established. Radiation therapy for ONB is challenging because of the proximity of ONBs to critical organs. Proton-beam therapy can provide better dose distribution compared with X-ray irradiation because of its physical characteristics, and is deemed to be a feasible treatment modality. METHODS AND MATERIALS: A retrospective review was performed on 14 patients who underwent PBT for ONB as definitive treatment at the National Cancer Center Hospital East (Kashiwa, Chiba, Japan) from November 1999 to February 2005. A total dose of PBT was 65 cobalt Gray equivalents (Gy(E)), with 2.5-Gy(E) once-daily fractionations. RESULTS: The median follow-up period for surviving patients was 40 months. One patient died from disseminated disease. There were two persistent diseases, one of which was successfully salvaged with surgery. The 5-year overall survival rate was 93%, the 5-year local progression-free survival rate was 84%, and the 5-year relapse-free survival rate was 71%. Liquorrhea was observed in one patient with Kadish's stage C disease (widely destroying the skull base). Most patients experienced Grade 1 to 2 dermatitis in the acute phase. No other adverse events of Grade 3 or greater were observed according to the RTOG/EORTC acute and late morbidity scoring system. CONCLUSIONS: Our preliminary results of PBT for ONB achieved excellent local control and survival outcomes without serious adverse effects. Proton-beam therapy is considered a safe and effective modality that warrants further study.

Dummy run for a phase II multi-institute trial of chemoradiotherapy for unresectable pancreatic cancer: inter-observer variance in contour delineation.

UNLABELLED: The aim of this study was to examine the interobserver variance in delineating the contour of unresectable pancreatic cancer for chemoradiotherapy. PATIENTS AND METHODS: CT images of two cases of unresectable pancreatic tumors (head and body cancer) were sent to eight radiation therapy facilities in a CD-ROM. Gross tumor volume (GTV) and planning target volume (PTV) were delineated using the radiotherapy treatment planning system (RTP) of the respective facilities. The mean and variance of the GTV and PTV of 11 plans by the eight facilities were analyzed. RESULTS: The respective mean volumes of the GTV of pancreatic head and body cancer cases were 34.8 cm3 (SD, 30.4; median, 31.8; range, 13.5-122 cm3) and 73.4 cm3 (SD, 28.1; median, 67.9; range, 46.3-152 cm3). The ratios of the largest to the smallest contoured GTV were 9 and 3, respectively. The corresponding average volumes of PTV were 148 cm3 (SD, 84.3; median, 129; range, 69.6-363 cm3) and 240 cm3 (SD, 79.8; median, 227; range, 148-420 cm3). The ratios of the largest to the smallest contoured volume were 5 and 2.8 for PTV delineation, respectively. CONCLUSION: Dummy run using CD-ROM is possible on a multi-institute scale but also disclosed interobserver variance. Unified protocol interpretation to reduce inter-observer variance is therefore essential for successful multi-institute clinical trials.

Accelerated radiotherapy and larynx preservation in favorable-risk patients with T2 or worse hypopharyngeal cancer.

OBJECTIVE: To evaluate the advantage of accelerated fractionation radiotherapy for patients with hypopharyngeal cancer requiring total laryngectomy. METHODS: Seventy patients with previously untreated, technically resectable hypopharyngeal cancer who received larynx-preserving treatment with radiotherapy between April 1992 and June 2004 were analyzed. No patients had previous history of other malignancy or poor performance status that would possibly affect the outcomes. A total RT dose of > or = 60 Gy/6 weeks was determined depending on the tumor clearance during treatment before December 1998, and fixed to 70 Gy in all patients thereafter. Accelerated fractionation (70 Gy/<49 days) was completed in 35 patients during the latter period. Concomitant platinum-based chemotherapy was used in 41 patients after May 1998. RESULTS: Local control rates at 2 years were 72 and 68% for patients with T2 and T3/T4 disease, respectively. Patients who had received 70 Gy/<49 days achieved a better local control rate than those who had received other, more conservative total dose/overall treatment time with statistical significance (91% versus 50% at 2 years, P < 0.001). Multivariate analysis involving 70 Gy/<49 days of radiotherapy, T-classification (T2 versus T3/4), and use of chemotherapy revealed that administering 70 Gy/<7 weeks was the only independent prognostic factor (P = 0.007) for better local control. CONCLUSIONS: Our experience in radiotherapy for hypopharyngeal cancer mirrored the results of previously conducted large randomized trials for various head and neck cancers. Encouraging local control in this study warrants prospective study to test the long-term oncological and functional outcome of larynx-preserving treatment in patients with advanced but resectable volume of this disease.

Influence of delayed tumor clearance on reliability of complete response rate in chemoradiotherapy for head and neck cancer.

OBJECTIVE: The relationship was studied between the timing of assessment of complete response and ultimate cure rate in the chemoradiotherapy of advanced head and neck cancer. METHODS: A retrospective review was conducted regarding tumor responses at 4 weeks, 3 months, and 6 months after concomitant chemoradiotherapy using cisplatin and 5-FU for 70 patients with stage III/IV squamous cell carcinoma of the oropharynx, hypopharynx and supraglottic larynx. Predictive values of tumor responses at these three time points for survival and tumor control at 2 years were tested using the chi-square test. RESULTS: Twelve (17%) patients achieved complete response (CR) at 4 weeks. Because of late regression or early recurrence, the CR rate changed to 18/70 (26%) and 24/70 (34%) at 3 and 6 months, respectively. CR or not at 6 months was significantly correlated with all survival endpoints (P < 0.001), but not those at 4 weeks and 3 months (P > 0.100). Kaplan-Meier estimate of overall survival at 5 years was 63% (95% CI 43-84%) for 24 CR patients at 6 months. CONCLUSION: CR rate at 6 months was a better surrogate endpoint than that at 4 weeks or 3 months in this series of patients.

Proton beam therapy for olfactory neuroblastoma.

PURPOSE: To clarify the efficacy and feasibility of proton beam therapy (PBT) for olfactory neuroblastoma (ONB). METHODS AND MATERIALS: We retrospectively reviewed 42 consecutive patients who received PBT with curative intent for ONB at National Cancer Center Hospital East from November 1999 to March 2012. RESULTS: Five patients (12%) had Kadish A disease, nine (21%) had Kadish B, and twenty-eight (67%) had Kadish C. All patients except one received a total dose of 65Gy (relative biological effectiveness: RBE) in 26 fractions. Twenty-four patients (57%) received induction and/or concurrent chemotherapy. The median follow-up for all eligible patients was 69months (7-186). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 100% and 80% for Kadish A, 86 and 65% for Kadish B, and 76% and 39% for Kadish C, respectively. The sites of the first progression were local in six patients (30%), regional in eight (40%), distant in two (10%), local and regional in two (10%), and local and distant in two (10%). Late adverse events of grade 3-4 were seen in six patients (ipsilateral visual impairment, 3; bilateral visual impairment, 1; liquorrhea, 1; cataract, 1). CONCLUSION: PBT was a safe and effective modality for ONB.