The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Background

Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.

Methods

The number, IFN-γ production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.

Results

The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-γ production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.

Conclusion

NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.     

Radiation injury of the parotid glands during treatment for head and neck cancer: assessment using dynamic contrast-enhanced MR imaging

The parotid gland is an important organ at risk of complications of radiotherapy for head and neck cancer. In this study, we examined the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of radiation injury to the parotid glands. DCE-MRI was performed before and 3 months after radiotherapy in patients treated for head and neck cancer. DCE-MRI was analyzed using the pharmacokinetic model proposed by Tofts and Kermode to produce three DCE parameters: k(trans), v(e) and v(p). These parameters were correlated with the dose of radiation delivered to the parotid glands and the degree of radiation-induced parotid atrophy. The mean radiation dose received by the parotid glands was 47.1 ± 6.6 Gy. All patients received concurrent chemotherapy. There was a significant rise in all three parameters after therapy (P < 0.0001). Baseline v(e) and v(p) and the post-treatment rise in v(e) correlated with parotid gland atrophy (P = 0.0008, 0.0003 and 0.0022, respectively). DCE-MRI has the potential to be used as a non-invasive technique for predicting and assessing radiation injury in the parotid glands.     

INDICATIONS FOR OPERATION IN LARYNGEAL CANCER

Improvements in the surgical treatment of laryngeal cancer by combined laryngectomy and radical neck dissection have given new importance to selection of the mode of treatment for various stages of disease at that site. To cast light on the subject, the cases of 63 patients with cancer of the larynx were reviewed. Twenty-one of them were operated on for recurrence after radiation therapy; and 42 were treated surgically at the outset, 36 of them having combined laryngectomy and radical neck dissection. In almost 80 per cent of the patients the lesion was extrinsic.In the entire series, 51 patients had combined operations, and in 41 of them the cervical lymph nodes were positive for metastasis.Reports in the literature also make note of a very high incidence of cervical node metastasis not only in cases of extrinsic cancer, but also in those in which the lesion is intrinsic.Because of the frequency of cervical node spread, and its occult nature, choice between radiation and surgical operation must be made after candid, critical appraisal of the individual condition in each patient.     

功能与分子影像在头颈部肿瘤放射治疗计划和疗效评价中的应用

目前临床普遍采用功能与分子影像检测手段能来评价头颈部肿瘤的放射治疗计划和疗效,可指导个体化治疗从而提高疗效。文章概述了功能与分子影像技术CT,MRI,PET-CT,超声检测技术在头颈部肿瘤放射治疗计划制定和疗效评价中的应用进展。结果显示,不同分子影像检测方法如在检查时机的选择、诊断和鉴别诊断的价值、观察放射治疗后肿瘤的残存和复发、预测放射治疗效果、指导后续治疗等方面均可起到重要作用。采用图像融合技术进行联合应用,如PET-CT和MRI-CT等,可提高检测的准确率。临床医生需在常规影像学手段的基础上,根据头颈部肿瘤患者病情和治疗方法的不同选用正确的功能和分子影像检测手段,更好地指导制定放射治疗计划及综合评价放射治疗后的疗效。     

Breast reconstruction with postmastectomy radiation therapy: current issues

Two recent trials have demonstrated superior locoregional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of postmastectomy radiation therapy to mastectomy and chemotherapy. Based on these results, there has been an increased use of postmastectomy in patients with early-stage breast cancer. The inability to determine which patients will require postmastectomy radiation therapy has increased the complexity of planning for immediate breast reconstruction. There are two potential problems with performing an immediate breast reconstruction in a patient who will require postmastectomy radiation therapy. One problem is that postmastectomy radiation therapy can adversely affect the aesthetic outcome of an immediate breast reconstruction. Several studies have evaluated the outcomes of breast reconstructions that were performed before radiation therapy and have revealed a high incidence of complications and poor aesthetic outcomes. Furthermore, these studies have found that often an additional flap is required to restore breast shape and symmetry. The other potential problem is that an immediate breast reconstruction can interfere with the delivery of postmastectomy radiation therapy. During planning for immediate breast reconstruction, it is imperative to carefully review the stage of disease and the likelihood the patient will require postmastectomy radiation therapy. Unfortunately, the ability to detect and predict the presence or extent of axillary lymph node involvement is limited, and the need for postmastectomy radiation therapy is usually not known until after mastectomy. In all cases of decision making regarding possible postoperative radiation therapy and whether or not to perform immediate breast reconstruction, the situation should be discussed at a multidisciplinary conference or addressed among the various medical, surgical, and radiation teams, with active participation by the patient. Immediate breast reconstruction probably should be avoided in patients known to require postmastectomy radiation therapy and delayed until it is certain the therapy will be needed in patients who may require the therapy.     

Prostate cancer: progression of prostate-specific antigen after external beam irradiation

This paper is concerned with the development of a stochastic path of prostate-specific antigen (PSA) level after radiation treatment for prostate cancer. PSA is a biomarker for prostate cancer, higher levels of which indicate the seriousness of the cancer progression. Following the deterministic modeling of the data by the previous authors, Cox et al., this paper is concerned with the theoretical knowledge that could be gained by the stochastic modeling in discrete form of the PSA path over time. The expected value of the PSA level is computed and compared with the deterministic model and it is found that they are the same for about the first year after radiation therapy. The American Society for Therapeutic Radiology has set a consensus panel definition of biochemical failure following radiation therapy: the rise in three consecutive levels of PSA is considered to be a failure of the radiation therapy. Knowledge of the path of PSA presented in this paper would be useful in the management of the radiation treatment and in particular assessing quantitatively any clinically based policy for defining recurrence after radiation therapy. Application of the model is illustrated by fitting it to clinical data available in the University of Michigan cancer center.     

EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition

Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway.     

The Rapalogue,CCI-779, Improves Salivary Gland Function following Radiation

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5^f/f; Aqp5-Cre, Atg5^+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.     

Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction

BackgroundXerostomia, or dry mouth, is a common side effect of head and neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Adult stem cells are the ultimate source for replenishment of salivary gland tissue. Bone marrow–derived mesenchymal stromal cells (BM-MSCs) are a viable cell-based therapy for xerostomia. We have undertaken studies enabling U.S. Food and Drug Administration Investigational New Drug status, demonstrating the normal phenotype, intact functionality, and pro-growth secretome of interferon-γ (IFNγ)-stimulated BM-MSCs taken from patients with head and neck cancer who have undergone radiation ± chemotherapy. Here we present the protocol of MARSH, a first-in-human clinical trial of bone marrow–derived, IFNγ-activated BM-MSCs for the treatment of radiation-induced xerostomia.MethodsThis single-center phase 1 dose-escalation with expansion cohort, non–placebo-controlled study will assess the safety and tolerability of BM-MSCs for the treatment of radiation-induced xerostomia in patients who had head and neck cancer. The phase 1 dose-escalation study will be a 3 + 3 design with staggered enrollment. A total of 21 to 30 subjects (9 to 18 in phase 1 study, 12 in expansion cohort) will be enrolled. The primary endpoint is determining the recommended phase 2 dose (RP2D) of IFNγ-stimulated BM-MSCs to enable further studies on the efficacy of BM-MSCs. Patients’ bone marrow will be aspirated, and BM-MSCs will be expanded, stimulated with IFNγ, and injected into the submandibular gland. The RP2D will be determined by dose-limiting toxicities occurring within 1 month of BM-MSC injection. Secondary outcomes of saliva amounts and composition, ultrasound of salivary glands, and quality of life surveys will be taken at 3-, 6-, 12-, and 24-month visits.DiscussionAutotransplantation of IFNγ-stimulated BM-MSCs in salivary glands after radiation therapy or chemoradiation therapy may provide an innovative remedy to treat xerostomia and restore quality of life. This is the first therapy for radiation-induced xerostomia that may be curative.Trial registrationWorld Health Organization International Clinical Trials Registry Platform: NCT04489732     

Dose to swallowing structures and dysphagia in head and neck Intensity Modulated Radiation Therapy – A long term prospective analysis

AimTo analyse the long term swallowing function in head and neck cancer patients and correlate with the dose to midline swallowing structures.BackgroundThe use of concurrent chemo radiation (CRT) as the present standard of care resulted in high rates of early and late toxicities. Dysphagia, aspiration, and xerostomia are early as well as late effects of radiation. Not many studies on the dysphagia scores during radiation and follow-up period have correlated dose to the swallowing structures, hence this study.Materials and MethodsHistologically proven head and neck cancer patients treated with intensity modulated radiation therapy were accrued in this study. The pharyngeal constrictors, larynx and cervical oesophagus were contoured and labelled as midline swallowing structures. The volume of the midline swallowing structures which were outside the PTV was delineated separately and was given a mean dose constraint of 45 Gy. Dysphagia was assessed at baseline, weekly intervals during irradiation and follow-up at six years. The dose to the structures for swallowing was correlated with degree of dysphagia.ResultsThere was a gradual increase in the dysphagia grade during the course of radiation. There was a significant recovery of late dysphagia compared to dysphagia during the completion of radiation therapy in patients who received <45 Gy to the swallowing structures (p < 0.0001).ConclusionGiving a constraint to the swallowing structure and limiting it to <45 Gy resulted in earlier recovery of swallowing function resulted in good physical, mental and social well being of the patients when compared to those who received >45 Gy.     

The importance of the age factor in cancer vaccination at older age

Cancer is an age-related disease, and with the graying of the society there is an increasing need to optimize cancer management and therapy to elderly patients. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. Therefore, research is needed to establish whether age-specific tumor-immunological variables permit optimal use of cancer vaccines and therapy in the elderly. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, and the results of cancer vaccination in preclinical models at young and old age. Finally, new directions that may lead to effective cancer vaccination at older age will be proposed.     

p53 serum antibodies as prognostic indicator in head and neck cancer

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer. Received: 5 December 1996 / Accepted: 4 January 1997     

Quality of life and disease-specific functional status following microvascular reconstruction for advanced (T3 and T4) oropharyngeal cancers

In an effort to evaluate quality-of-life benefits of ablative head and neck cancer surgery and microvascular reconstruction, a longitudinal study was undertaken in which patients with T3 or T4 oropharyngeal cancers without systemic metastases at presentation were administered both general and disease-specific quality-of-life instruments preoperatively and postoperatively. In an initial prospective pilot study, 17 cancer patients were evaluated both preoperatively and postoperatively using the Medical Outcomes Short-Form Health Survey questionnaire (SF-36) and the Performance Status Scale for Head and Neck Cancer Patients. In the second part of the study, the need was recognized for a different disease-specific measure, for more frequent intervals of longitudinal follow-up (rather than be limited by a single data collection point), and for a noncancer control group. Since then, 17 more cancer patients were evaluated in the second part of the study and were compared with patients who had similar reconstructions after suffering head and neck trauma and also with age-matched controls. Instead of the performance status scale, the University of Washington Head and Neck Quality of Life questionnaire was substituted. Interval assessments were done at 1, 3, 6, and 12 months and preoperatively. Whereas many of the general and disease-specific quality of life subclasses initially worsened following extensive surgery and radiation therapy, most returned to the preoperative baseline by 6 months following conclusion of treatment and surpassed pretreatment values at 1 year. It can be concluded, based on this study, that large resections and reconstructions for head and neck cancer patients are justified in terms of outcome; the resection controls the local disease, and the microvascular reconstruction restores quality of life and functional status.     

Neoadjuvant chemotherapy in head and neck cancer

BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients' status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.     

Adenoviral gene therapy, radiation, and prostate cancer

Viral gene therapy has exceptional potential as a specifically tailored cancer treatment. However, enthusiasm for cancer gene therapy has varied over the years, partly owing to safety concerns after the death of a young volunteer in a clinical trial for a genetic disease. Since this singular tragedy, results from numerous clinical trials over the past 10 years have restored the excellent safety profile of adenoviral vectors. These vectors have been extensively studied in phase I and II trials as intraprostatically administered agents for patients with locally recurrent and high-risk local prostate cancer. Promising therapeutic responses have been reported in several studies with both oncolytic and suicide gene therapy strategies. The additional benefit of combining gene therapy with radiation therapy has also been realized; replicating adenoviruses inhibit DNA repair pathways, resulting in a synergistic sensitization to radiation. Other, nonreplicating suicide gene therapy strategies are also significantly enhanced with radiation. Combined radiation/gene therapy is currently being studied in phase I and II clinical trials and will likely be the first adenoviral gene therapy mechanism to become available to urologists in the clinic. Systemic gene therapy for metastatic disease is also a major goal of the field, and clinical trials are currently under way for hormone-resistant metastatic prostate cancer. Second- and third-generation "re-targeted" viral vectors, currently being developed in the laboratory, are likely to further improve these systemic trials.     

Monolayer cell cultures as target cells for the study of lymphocyte cytotoxicity in cancer patients.

Lymphocytotoxicity using S3-Hela target cells has been studied in 20 cancer patients treated with ionizing radiation (head and neck, lung and breast cancers). Monolayer cultures of Hela cells were marked with radioactive 51 Chromium and cultured with non stimulated or phytohemagglutinin (PHA) stimulated lymphocytes. This study shows a spontaneous decrease of lymphocytotoxicity in cancer patients as compared with normal subjects and an immunodepressive effect of radiotherapy. We observe a significant decrease of lymphocytotoxicity for either stimulated or non-stimulated lymphocytes at the end of radiation treatment. Moreover one month after completion of radiotherapy a possible repair of a lymphocytoxicity seems to be related with a short-term (6 months) good prognosis.     

The efficiency of the radiobiological and clinical of the intraoperative radiation therapy in combination with distant gamma-radiation therapy of malignant tumors

The efficiency of the radiobiological and the clinical planning of the combination of the intraoperative radiation therapy (IORT) and the external beam radiation therapy (EBRT) was assessed according to the incidence of local recurrences and to the level of radiation-induced damages during 5 years for patients with malignant tumors of head and neck, lung and soft tissues. Criteria of radiobiological planning for performing IORT + EBRT using the modified model of TDF (time-dose-fractionation) for calculating a single IORT dose and total radiation doses was defined among 169 patients of the studied group. The control group included 115 patients who were treated with surgery followed by photon radiation therapy at the total dose of 40-45 Gy. The Clinical critetia for performing the combined treatment with IORT and EBRT were such like: locally-advanced tumors, multicentrical location of tumor sites and the necessity of the increasing of the total doses of the combination of IORT and EBRT. The Average rates of total doses of IORT and EBRT were 67 +/- 2.1 Gy for patients with cancer of nasal cavity and of accessory nasal sinus, 50 +/- 1.8 Gy for patients with oral cavity cancer, 60 +/- 0.7 Gy for patients with lung cancer and 75 +/- 2.0 Gy for patients with sarcomas of soft tissues. Radiation-induced damages for normal tissues such as mandible osteomyelitis, neuritis and pathological bone fracture occurred among 16.8% of patients from the studied group if the TDF factor was exceeded over 100 conventional units. The combined treatment with IORT and EBRT resulted the significant reduction of recurrence rate among 5-year as compared with the combined treatment fot the control group: 37.5 +/- 5.3% and 65 +/- 5.1% of patients with cancer of nasal cavity and accessory nasal sinus; 55.8 +/- 6.3% and 80 +/- 5.9% of patients with oral cavity cancer; 57.8 +/- 6.7% and 75 +/- 5.8% of patients with non-small cell lung cancer and 32.7 +/- 6.1% and 72 +/- 6.7% of patients with sarcomas of soft tissues, respectively. The use of criteria for radiobiological and clinical planning of the combined treatment with IORT and EBRT promotes the improvement of long-term treatment results.     

Scattered dose to radiosensitive organs and associated risk for cancer development from head and neck radiotherapy in pediatric patients

The purpose of this study was to measure the scattered dose to out-of-field organs from head and neck radiotherapy in pediatric patients and to estimate the risk for second cancer induction to individual organs. Radiotherapy for thalamic tumor, brain tumor, acute leukemia and Hodgkin's disease in the neck region was simulated on 5 and 10-year-old pediatric phantoms with a 6 MV photon beam. The radiation dose to thyroid, breast, lung, stomach, ovaries, bladder, liver, uterus, prostate and colon was measured using thermoluminescent dosimeters. The methodology, provided by the BEIR VII report was used for the second cancer risk estimations. Peripheral dose range for a simulated 5-year-old patient was 0.019%–1.572% of the given tumor dose. The corresponding range at the advanced patient age was reduced to 0.018%–1.468%. The second cancer risk per fraction for male patients varied from 3 to 215 per 1,000,000 patients depending upon the age at the time of exposure, primary cancer site and organ scattered dose. The corresponding risk for females was 1–1186 per 1,000,000 patients. The higher risk values were found for breast, thyroid and lung cancer development. The current data concerning the risk magnitude for developing subsequent neoplasms to various out-of-field organs may be of value for health care professionals in the follow-up studies of childhood cancer survivors.     

Diffusion Magnetic Resonance Imaging: An Imaging Treatment Response Biomarker to Chemoradiotherapy in a Mouse Model of Squamous Cell Cancer of the Head and Neck

For the treatment of squamous cell cancer of the head and neck (SCCHN), the assessment of treatment response is traditionally accomplished by volumetric measurements and has been suggested to be prognostic for an eventual response to treatment. An early evaluation response during the course of radiation therapy could provide an opportunity to tailor treatment to individual patients. Diffusion magnetic resonance imaging (MRI) allows for the quantification of tissue water diffusion values, thus treatment-induced loss of tumor cells will result in the increase in water mobility at the microscopic level, which can be detected as an increase in tumor diffusion values before any volumetric changes occur. We evaluated the use of diffusion MRI as an imaging biomarker of treatment response in an orthotopic mouse model of SCCHN. Mice with murine squamous cells expressing the yeast transgene cytosine deaminase were treated with 5-fluorocytosine (5FC), ionizing radiation, and combined therapy and were compared with control animals both during and after treatment for changes in tumor volumes, diffusion values, and survival. Radiation therapy had minimal effect on volumetric growth rate, diffusion, or survival. Although 5FC and combination treatment resulted in similar reductions in tumor volumes, the combination treatment elicited a much greater increase in tumor diffusion values, which correlated with improved survival. Thus, diffusion MRI as an imaging biomarker has a potential for early evaluation of the response to chemoradiation treatment in SCCHN.     

Apport d’un nouveau score visuel en TEP/TDM au 18Fluorodeoxyglucose (18FDG) lors des récidives ganglionnaires de cancer ORL après traitement initial

New visual score in PET/CT 18Fluorodeoxyglucose (¹⁸FDG) to evaluate lymph node recurrence of head and neck cancer after initial treatment. Neck dissection for node recurrence of head and neck cancer is known for important morbidity after initial radiation therapy. ¹⁸FDG PET/CT in this situation looks interesting but needs standardized interpretation. Our objective was to develop a PET/CT interpretation method in suspicious locoregional head and neck recurrence. Twenty-seven patients with suspicious lymph node recurrence after initial radiation ± chemotherapy for head and neck cancer were retrospectively included. ¹⁸FDG PET/CT was performed before neck dissection and histological data. Initial PET records, binary visual scale, five-point visual scale “Deauville like” and semi-quantitative index were assessed by 2 reviewers. A lymph node recurrence was confirmed in 19 patients (70%) based on histological results. PET records analysis found 6 false positive (FP), 2 true negative (TN) and 19 true positive (TP), with a sensibility (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 100%, 25%, 76% and 100%, respectively. Binary visual scale reclassified 1/6 FP. “Deauville like” criteria, reclassified 4/6 FP with the first reviewer (P < 0.001) and 5/6 with the second (P < 0.002), improving Sp and PPV of 66% and 95%, respectively. Kappa concordance coefficient for “Deauville like” scale was 0.88. Semi-quantitative index like SUVmax, SUVmean, SUVpeak, MTV, TLG and SAM showed no statistical value. Those preliminary results warrant a standardized visual scale, particularly the “Deauville like” criteria for ¹⁸FDG PET/CT interpretation in suspected lymph node recurrence of head and neck cancer.