Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

The Utility of Glasgow Prognostic Score and Palliative Prognostic Index in Patients With Head and Neck Squamous Cell Carcinoma Under Palliative Care.

OBJECTIVES: Palliative care patients with head and neck squamous cell carcinoma (HNSCC) often experience dysphagia and airway trouble; thus, each patient requires a specific palliative care plan based on their prognostication. However, no established specific prognostic tool performed on the day of starting end-of-life care is available for such patients. We assessed the accuracy of Glasgow prognostic score (GPS) and palliative prognostic index (PPI) and their combination to establish a specified prognostic tool for patients with HNSCC in end-of-life setting. METHODS: A retrospective clinical chart review was undertaken on patients with HNSCC in end-of life setting who were decided in Kagawa University Hospital and National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. The patients were divided into 2 categories according to GPS (0-1 and 2) and PPI (groups A-B and C). These were combined into 4 categories (PPI group A-B and GPS score 0-1: good; PPI group A-B and GPS score 2: intermediate; PPI group C and GPS score 2: poor; and PPI group C and GPS score 0-1: others). The survival curves were compared for the former 3 categories. RESULTS: The median survival of the scores 0-1 and 2 on GPS were 114 (72-148) and 39 (25-52) days, respectively (P < .01). These of groups A-B and C on PPI were 79 (64-99) and 16 (9-29) days, respectively (P < .01). The median survival of the good, intermediate, and poor categories was 127 (73-149), 64 (44-80), and 15 (9-27) days, respectively (P < .01 among all categories). CONCLUSIONS: In this study, the survival of terminally ill patients with HNSCC can be predicted by the GPS, PPI, and their combination with sufficient probability.

Comparison of the accuracy of clinical prediction of survival and palliative prognostic index for patients with head and neck squamous cell carcinoma in the end-of-life setting.

OBJECTIVE: In the end-of-life stage of head and neck squamous cell carcinoma (HNSCC), predicting survival is essential to determine treatment procedure and place of care. Several reports have compared actual survival (AS) and clinical prediction of survival (CPS), a subjective prognostic prediction by attending physicians. However, specific studies focusing on patients with HNSCC are limited. Likewise, a comparison of the accuracy of CPS and palliative prognostic index (PPI), a prognostic tool using subjective assessment, has not been sufficiently investigated. This study aimed to clarify the correlation between AS and CPS/PPI and compare the accuracy of CPS and PPI in end-stage HNSCC. METHODS: This retrospective study included patients with HNSCC in the end-of-life setting. Patients were recruited from the National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. Data on basic demography and clinical parameters when patients decided to start end-of-life care at the head and neck oncology division were collected. We examined the correlation between AS and CPS using Spearman's correlation coefficients. The area under the receiver operating characteristic curve of CPS and PPI for 30-day survival prediction were compared for predictive accuracy. RESULTS: Among 98 eligible patients, 59 patients were enrolled in this study and analyzed. Of the 59 patients, CPS and PPI were calculated for 30 patients, whereas, only the PPI was calculated for 29 patients. The median AS and CPS were 35 (IQR: 9-73) days and 30 (IQR: 7-83) days, respectively. CPS and PPI (30 cases) were moderately correlated (r = 0.72, p<0.01). AS and CPS/PPI (30 cases) were significantly correlated (p<0.01) and showed a strong correlation (r = 0.86 and 0.80, respectively). In the 30-day survival prediction, the AUROCs of CPS and PPI (30 cases) were 0.967 (95%CI: 0.919-1) and 0.884 (95%CI: 0.767-1), respectively. Both CPS and PPI (30 cases) showed high accuracy in predicting the 30-day prognosis, with no significant difference (p = 0.077). The AUROC of PPI (59 cases) was 0.840 (95%CI: 0.711-0.969). CONCLUSIONS: AS and CPS/PPI showed significant correlations. The high accuracy of CPS may have been influenced by the fact that multiple head and neck cancer specialists at a comprehensive cancer center estimated CPS. Both CPS and PPI showed high prognostic accuracy in predicting 30-day survival. This suggests that PPI is useful in centers among physicians and healthcare workers unfamiliar with head and neck cancer.

Otorhinolaryngologists/head and neck surgeons' knowledge, attitudes, and practices regarding fertility preservation in young cancer patients treated with chemotherapy: an anonymous questionnaire survey.

BACKGROUND: It is well known that chemotherapy for adolescent and young adult (AYA) patients with cancer can reduce fertility regardless of the regimen. A decline in fertility greatly affects the quality of life of cancer survivors in the AYA age group; however, few patients are thought to be receiving fertility preservation measures. METHODS: A questionnaire survey was conducted to assess the current understanding and consideration of fertility among otorhinolaryngologists/head and neck surgeons who treat AYA patients with cancer, and to inform them of the guidelines for fertility preservation. A total of 275 otorhinolaryngologists/head and neck surgeons working at our hospital in Ehime, Japan, six neighboring universities, and their affiliated facilities were included in this study. The questionnaire was mailed and requested to be returned by fax. Twenty questions were asked about respondents' years of experience as physicians, specialties, experience in medical care and chemotherapy for AYA patients with cancer, and knowledge and experience in fertility reduction measures. RESULTS: Although 58.7% of the physicians were aware that cryopreservation of eggs and sperm prior to chemotherapy was recommended, only 7 out of 40 physicians (17.5%) had referred AYA patients with cancer to an appropriate medical facility (department) after obtaining informed consent for chemotherapy. CONCLUSIONS: Although fertility preservation has been discussed at professional conferences and seminars, consideration and actions in the field of otorhinolaryngology/head and neck surgery have not been sufficient. We hope that the results of this survey will help raise awareness of fertility preservation.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

CONCLUSION: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. OBJECTIVES: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. METHODS: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. RESULTS: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Prognostic value comparison between (18)F-FLT PET/CT and (18)F-FDG PET/CT volume-based metabolic parameters in patients with head and neck cancer.

PURPOSE: The present study compared the potential of pretreatment 3'-deoxy-3'-[F]-fluorothymidine (F-FLT) uptake parameters and those of F-FDG to predict the clinical outcome of head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: A total 53 patients undergoing pretreatment F-FLT PET/CT and F-FDG PET/CT from May 2006 to April 2013 were evaluated. The SUVmax, metabolic tumor volume (MTV), total lesion glycolysis, and total lesion proliferation (TLP) were determined semiquantitatively. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: In univariate analyses, F-FLT SUVmax, MTV, TLP, F-FDG MTV, and total lesion glycolysis correlated with locoregional control (P = 0.02, P = 0.0007, P = 0.0001, P = 0.007, and P = 0.013, respectively). Clinical T stage, F-FLT SUVmax, MTV, TLP, and F-FDG SUVmax correlated with overall survival (P = 0.012, P = 0.0057, P = 0.0018, P = 0.0012, and P = 0.047, respectively). On multivariate analyses, F-FLT TLP was an independent factor for locoregional control (P = 0.002; hazards ratio [HR], 5.13; 95% confidence interval [CI], 1.81-14.54), as were F-FLT SUVmax and MTV for overall survival (P = 0.021; HR, 3.47; 95% CI, 1.2-10.01 and P = 0.029; HR, 3.17; 95% CI, 1.12-8.95). CONCLUSIONS: Pretreatment F-FLT PET/CT volume-based metabolic parameters are superior prognostic predictors to those of F-FDG PET/CT. F-FLT SUVmax and MTV can provide important prognostic information for patients with head and neck squamous cell carcinomas administered with chemoradiotherapy.

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

OBJECTIVE: The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. PATIENTS AND METHODS: A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). RESULTS: The mean (± SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97 ± 3.16, 6.71 ± 3.75, 10.05 ± 5.37, 7.31 ± 8.05 and 44.95 ± 52.82, respectively. In univariate analyses, N category was associated with OS (P = 0.037). Increased MTV ≥13 ml was associated with decreased LRC and OS (P < 0.0001). TLP ≥69.3 g was also linked with both LRC and OS (P = 0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P = 0.035 and 0.049, respectively). CONCLUSIONS: Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients.

OBJECTIVE: Diagnostic efficacy of (18)F-FLT PET was compared with that of (18)F-FDG PET regarding second primary cancers and distant metastases of head and neck squamous cell cancers (HNSCCs). METHODS: A total of 88 patients with HNSCCs were qualitatively examined with FLT PET and FDG PET for regions of focally increased metabolism. Final diagnoses of second primary cancer and distant metastasis were established on the basis of histological findings or clinical follow-up. RESULTS: FDG PET had 1 false-negative finding with lung metastasis, and FLT PET had 4 false-negative findings with 1 liver metastasis, 1 bone metastasis, and 2 lung metastases. There were no false-positive findings with FLT PET in contrast to 9 with FDG PET (1 in lung, 4 in mediastinum, 1 in rectum, and 3 in stomach). Overall accuracy of FDG PET and FLT PET for pretreatment metastasis staging was 92% and 98%, respectively. Five distant metastases in 3 patients occurred after the initiation of chemoradiotherapy. FLT PET missed 2 metastatic lesions (1 in liver and 1 in lung), whereas FDG PET could not discriminate intracranial metastasis because of FDG uptake in the brain. CONCLUSIONS: FLT PET does not appear to be recommendable to replace FDG PET for pretreatment metastasis staging in HNSCC cases because of its lower sensitivity and higher background activity in the liver and bone marrow. However, it might provide additional diagnostic specificity and biological information.

Changes in (18)F-fluorothymidine and (18)F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy.

OBJECTIVE: This study compared change of (18)F-fluorothymidine (FLT) uptake with that of (18)F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy. METHODS: Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated. RESULTS: According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET. CONCLUSION: FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.

Comparison of ( 18 ) F-FLT PET and ( 18 ) F-FDG PET for detection of cervical lymph node metastases in head and neck cancers.

CONCLUSION: Despite low uptake of tracer, 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET could detect cervical lymph node metastases as well as 2-deoxy-2-(18)F-fluoro-d-glucose (FDG) PET. OBJECTIVE: The diagnostic efficacy of FLT PET was compared with that of FDG PET regarding nodal staging of head and neck squamous cell cancers. METHODS: Twenty-three patients were examined with FLT PET and FDG PET. PET images were evaluated qualitatively for regions of focally increased metabolism and maximum standardized uptake values (SUV) were calculated for semiquantitative analysis. RESULTS: The mean (± SD) FLT SUV in visualized metastatic lymph nodes was 4.8 ± 2.9 as compared with 6.9 ± 4.9 for FDG SUV (p < 0.001). Significant correlations were found between the area of metastatic lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p < 0.0001). The false-positive (over-staged) and false-negative (under-staged) rates for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively. Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes measuring more than 9 mm in short-axis diameter were correctly detected by FLT PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph node metastases ≤ 9 mm in short-axis diameter and tumor deposits < 5 mm.

Usefulness of 3'-deoxy-3'-18F-fluorothymidine PET for predicting early response to chemoradiotherapy in head and neck cancer.

UNLABELLED: This study compared the utility of 3'-deoxy-3'-(18)F-fluorothymidine PET ((18)F-FLT PET) with that of (18)F-FDG PET for assessment of the early locoregional clinical outcomes of chemoradiotherapy for head and neck squamous cell carcinomas. METHODS: From May 2006 to September 2010, 28 patients with head and neck squamous cell carcinomas underwent (18)F-FLT and (18)F-FDG PET before radiation therapy (RT), 4 wk after the initiation of RT, and 5 wk after completion of RT. PET images were evaluated qualitatively for regions of focally increased metabolism and were analyzed in relation to residual accumulation and local disease control. RESULTS: During RT, (18)F-FLT uptake decreased more significantly than (18)F-FDG uptake. (18)F-FLT accumulations disappeared in 34 of 54 lesions (63%), and negative predictive value was 97%. (18)F-FDG PET during RT also had a high negative predictive value (100%), but only 9 lesions (16%) showed complete absence of accumulation. The specificity and overall accuracy of (18)F-FLT PET were significantly higher than those of (18)F-FDG PET both during and after RT. In particular, high significance was attributable to the results of the evaluations of primary lesions. There were significant differences in 3-y local control between the residual-accumulation and no-accumulation groups on both posttreatment (18)F-FLT PET (P < 0.0001) and posttreatment (18)F-FDG PET (P = 0.0081). CONCLUSION: (18)F-FLT PET during RT and early follow-up facilitates the selection of optimal further therapy and the prediction of outcomes.

Early prediction of local control in head and neck cancer after chemoradiotherapy by FDG-PET.

OBJECTIVE: To determine the utility of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography (FDG-PET) for assessment of early locoregional clinical outcome of chemoradiotherapy for head and neck squamous cell carcinomas (HNSCCs). METHODS: From July 2002 to July 2008, a total of 35 patients with HNSCCs underwent FDG-PET before and between 4 and 7 weeks (median: 5 weeks) after the end of concurrent chemoradiotherapy. FDG uptake of primary sites and metastatic lymph nodes was measured as standardized uptake values (SUVs) and was analyzed in relation to local control. RESULTS: Visual inspection showed a sensitivity of 88.2% and a negative predictive value of 93.1%, but the positive predictive value was only 37.5%. Setting a posttreatment SUV of 3.0 and percentage change of 60 as cut-off values, positive predictive value increased to 81.3% and overall accuracy increased to 89.9% using the combined analysis of these two parameters. The local control rate was not associated with T, the N category, or the tumor node metastasis stage. In contrast, combined analysis of the posttreatment SUV and the percentage change in SUV was a useful indicator of locoregional control. In particular, combined evaluation of SUVs was very effective for assessment of therapeutic effects with reference to metastatic lymph nodes. CONCLUSION: Early follow-up with FDG-PET is thus considered helpful further in choosing optimal therapy and for making an accurate prognosis.

Comparison of FLT-PET and FDG-PET for visualization of head and neck squamous cell cancers.

PURPOSE: We compared 3'[F-18]fluoro-3'-deoxythymidine (FLT) positron emission tomography (PET) and 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) for PET visualization of head and neck squamous cell cancers (HNSCCs) and evaluated which might better reflect proliferative activity as indicated by the Ki-67 index. PROCEDURES: A total of 43 patients with HNSCCs were examined with FLT-PET and FDG-PET. The PET images were evaluated qualitatively for regions of focally increased metabolism and for semiquantitative analysis the maximum standardized uptake value (SUV) was calculated. RESULTS: For depiction of primary tumours, the sensitivity of both approaches was 100%. The mean (± SD) SUV for FLT (5.65 ± 2.96) was significantly lower than that for FDG (10.9 ± 4.91; p < 0.0001). No significant differences were found for the T category. However, the mean (± SD) FLT SUV was significantly higher in poorly than in well-differentiated tumours (6.49 ± 3.13 vs. 4.2 ± 2.08; p < 0.04). Similarly, FDG SUVs in poorly and moderately differentiated tumours (12.72 ± 4.8 and 11.46 ± 4.64) were significantly higher than in well-differentiated tumours (7.45 ± 3.51; p < 0.004 and p < 0.02). No significant correlation was observed with the Ki-67 index for either. CONCLUSION: FLT-PET showed as high a sensitivity as FDG-PET for the detection of primary HNSCC lesions, although uptake of FLT was significantly lower than that of FDG.