Assessment of outcomes with delayed 18F-FDG PET-CT response assessment in head and neck squamous cell carcinoma

Objective:

To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC).

Methods:

105 patients who underwent a baseline and response assessment ¹⁸F-FDG PET-CT scan between 2008 and April 2013 were identified. ¹⁸F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes.

Results:

79 of 105 (75%) ¹⁸F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%).

Conclusion:

¹⁸F-FDG PET-CT 4 months post treatment has a very high NPV. A positive ¹⁸F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV.

Advances in knowledge:

Response assessment ¹⁸F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.     

Applications of diffusion-weighted magnetic resonance imaging in head and neck squamous cell carcinoma

In the head and neck, squamous cell carcinoma is one of the most common tumour types. Currently, the primary imaging modalities for initial locoregional staging are computed tomography and—to a lesser extent—magnetic resonance imaging, whilst [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography has additional value in the detection of subcentimetric metastatic lymph nodes and of tumour recurrence after chemoradiotherapy (CRT). However, dependency on the morphological and size-related criteria of anatomical imaging and the limited spatial resolution and FDG avidity of inflammation in metabolic imaging may reduce diagnostic accuracy in the head and neck. Diffusion-weighted magnetic resonance imaging (DWI) is a noninvasive imaging technique that measures the differences in water mobility in different tissue microstructures. Water mobility is likely influenced by cell size, density, and cellular membrane integrity and is quantified by means of the apparent diffusion coefficient. As such, the technique is able to differentiate tumoural tissue from normal tissue, inflammatory tissue and necrosis. In this article, we examine the use of DWI in head and neck cancer, focussing on technique optimization and image interpretation. Afterwards, the value of DWI will be outlined for clinical questions regarding nodal staging, lesion characterization, differentiation of post-CRT tumour recurrence from necrosis and inflammation, and predictive imaging towards treatment outcome. The possible consequences of adding DWI towards therapeutic management are outlined.     

Predictive value of diffusion-weighted magnetic resonance imaging during chemoradiotherapy for head and neck squamous cell carcinoma

Objective  

To evaluate diffusion-weighted (DWI) magnetic resonance imaging (MRI) for treatment prediction during chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNC).     

Hyaluronic acid carrier-based photodynamic therapy for head and neck squamous cell carcinoma

PurposeConventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment.Methods and ResultsPPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05).ConclusionsThese results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.     

头颈鳞癌的精准医疗研究进展

头颈鳞癌（head and neck squamous cell carcinoma,HNSCC）在全球范围内的发病率呈逐年上升趋势,尽管极力提高治疗水平,但其预后仍不理想。精准医疗时代,新的基因测序技术、液体活检技术、高分辨率成像技术以及分子病理学的进展,为HNSCC的精准诊断提供了良好的平台。而基于高通量基因测序及大数据分析等手段开发的精准细胞免疫治疗、个性化抗体偶联药物以及靶向人体微生物组药物等,为HNSCC的精准治疗提供了可靠的手段。作者综述了HNSCC精准诊断和精准治疗的相关研究进展。     

PET imaging of EGF receptors using [18F]FBEM-EGF in a head and neck squamous cell carcinoma model

Purpose  

To prepare and evaluate a new radiotracer for molecular imaging of cell surface receptors for epidermal growth factor (EGF).     

Whole-body-MR imaging including DWIBS in the work-up of patients with head and neck squamous cell carcinoma: A feasibility study

Objectives

To assess the feasibility of whole-body magnetic resonance imaging (WB-MRI) including diffusion-weighted whole-body imaging with background-body-signal-suppression (DWIBS) for the evaluation of distant malignancies in head and neck squamous cell carcinoma (HNSCC); and to compare WB-MRI findings with ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and chest-CT.

Methods

Thirty-three patients with high risk for metastatic spread (26 males; range 48–79 years, mean age 63 ± 7.9 years (mean ± standard deviation) years) were prospectively included with a follow-up of six months. WB-MRI protocol included short-TI inversion recovery and T1-weighted sequences in the coronal plane and half-fourier acquisition single-shot turbo spin-echo T2 and contrast-enhanced-T1-weighted sequences in the axial plane. Axial DWIBS was reformatted in the coronal plane. Interobserver variability was assessed using weighted kappa and the proportion specific agreement (PA).

Results

Two second primary tumors and one metastasis were detected on WB-MRI. WB-MRI yielded seven clinically indeterminate lesions which did not progress at follow-up. The metastasis and one second primary tumor were found when combining ¹⁸F-FDG-PET/CT and chest-CT findings. Interobserver variability for WB-MRI was κ = 0.91 with PA ranging from 0.82 to 1.00. For ¹⁸F-FDG-PET/CT κ could not be calculated due to a constant variable in the table and PA ranged from 0.40 to 0.99.

Conclusions

Our WB-MRI protocol with DWIBS is feasible in the work-up of HNSCC patients for detection and characterization of distant pathology. WB-MRI can be complementary to ¹⁸F-FDG-PET/CT, especially in the detection of non ¹⁸F-FDG avid second primary tumors.     

Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy.

In radiotherapy of head and neck cancer (HNC) and non-small cell lung cancer (NSCLC), hypoxia is known to be an important prognostic factor for long-term survival and local tumor control. The PET tracer (18)F-fluoromisonidazole (FMISO) allows noninvasive assessment of tumor hypoxia. This study analyzed whether FMISO PET could predict tumor recurrence after radiotherapy. METHODS: Forty patients with advanced HNC (n = 26) or NSCLC (n = 14) were studied before curative radiotherapy. Dynamic (0-15 min) and static PET scans were acquired up to 4 h after injection of 400 MBq of FMISO. Standardized uptake values (SUVs) and ratios to reference tissues (mediastinum or muscle) were calculated. In addition, time-activity curves up to 14 min after injection were classified visually. PET data were correlated with clinical follow-up data (presence or absence of local recurrence within 1 y), which were available for 21 patients. RESULTS: For HNC, patients with local recurrence could be separated from disease-free patients by SUV 4 h after injection (all recurrences had an SUV > 2). For NSCLC, no such correlation was observed. The tumor-to-muscle ratios (T/Mu) and tumor-to-mediastinum ratios (T/Me) at 4 h after injection correlated with the risk of relapse in both tumor entities: All patients with a T/Me greater than 2.0 (NSCLC, n = 5) or with a T/Mu greater than 1.6 (HNC, n = 5) presented with tumor recurrence, whereas only 3 of the remaining 11 patients experienced recurrence (27%). Qualitative analysis of time-activity curves for 37 patients revealed 3 curve types (rapid washout, n = 9; intermediate [delayed washout], n = 12; and accumulation, n = 16). Eighteen patients categorized by curve type could be followed up: In 5 of 6 patients with an accumulation curve, disease recurred locally within 1 y, compared with 5 of 8 patients with a delayed-washout curve and 0 of 4 with a rapid-washout curve. CONCLUSION: Our results indicate that outcome after radiotherapy can be predicted on the basis of kinetic behavior of FMISO in tumor tissue. An accumulation-type curve, high SUV, and high T/Mu and T/Me at 4 h after injection are highly suggestive of an incomplete response to treatment and might be used to select patients for intensified therapy protocols.     

18F氟代脱氧葡萄糖PET-CT在头颈部肿瘤中的应用价值

PET-CT能对恶性肿瘤病灶进行准确定位,在头颈部肿瘤的诊断、定位及指导临床治疗方面与单纯PET相比具有明显的优势.PET和CT优势互补,有助于进一步提高诊断及分期的准确性和可信度,有助于鉴别正常生理性摄取、炎症和恶性肿瘤,同时可以更好地指导临床精确放疗.18F-氟代脱氧葡萄糖（18F-FDG）PET-CT在大多数头颈部恶性肿瘤的诊断方面虽然有明显的优越性,但在甲状腺和腮腺病灶的良恶性鉴别、急性炎症与肿瘤的鉴别等方面仍有不足.     

18F氟代脱氧葡萄糖PET-CT在头颈部肿瘤中的应用价值

PET-CT能对恶性肿瘤病灶进行准确定位,在头颈部肿瘤的诊断、定位及指导临床治疗方面与单纯PET相比具有明显的优势.PET和CT优势互补,有助于进一步提高诊断及分期的准确性和可信度,有助于鉴别正常生理性摄取、炎症和恶性肿瘤,同时可以更好地指导临床精确放疗.18F-氟代脱氧葡萄糖(18F-FDG)PET-CT在大多数头颈部恶性肿瘤的诊断方面虽然有明显的优越性,但在甲状腺和腮腺病灶的良恶性鉴别、急性炎症与肿瘤的鉴别等方面仍有不足.     

Role of DW-MRI and ADC value in monitoring therapy of head and neck squamous cell carcinoma

Aim

To evaluate role of DW-MRI and ADC value in monitoring therapy of head and neck squamous cell carcinoma (HNSCC).

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck

Background

Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART).

Patients and methods

Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400?mg/m²) and then with a weekly dosage of 250?mg/m² during HART. HART was started with a prescribed dosage of 2.0?Gy per day for 3 weeks, followed by 1.4?Gy twice daily to a total dose of 70.6?Gy to the gross tumour volume. CIS (40?mg/m²) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2?year progression-free survival (PFS).

Results

Between November 2007 and November 2010, a total of 74?patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37–69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2? and 5?year overall survival rates were 64 and 41%, the 2? and 5?year PFS rates were 45 and 32%, and the 2? and 5?year locoregional control rates were 47 and 33%, respectively.

Conclusion

The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.

     

Diffusion-weighted magnetic resonance imaging of head and neck squamous cell carcinomas

ObjectiveTo evaluate whether diffusion-weighted imaging (DWI) is a reliable technique to quantify microstructural differences between head and neck squamous cell carcinomas (SCC) and tumour-free soft tissue.Materials and methodsDWI was obtained from 20 patients with histologically proven, untreated head and neck SCC. DWI was acquired using a diffusion-weighted, navigated echo-planar imaging sequence with a maximum b-value of 800 s/mm². For an objective assessment of image quality, the signal-to-noise ratio (SNR) was calculated. Microstructural differences between vital tumour tissue and tumour-free soft tissue were quantified by calculating the apparent-diffusion-coefficients (ADC) on a pixel by pixel method.ResultsEcho-planar DWI provided good image quality in all patients (mean SNR 18.4). The mean ADC of SCC, (0.64 ± 0.28 × 10⁻³ mm²/s), was significantly (P < 0.0001) lower than that of the tumour-free soft tissue, (2.51 ± 0.82 × 10⁻³ mm²/s).ConclusionDWI is a reliable diagnostic tool to quantify the microstructural differences between vital tumour tissue and tumour-free soft tissue in patients with head and neck SCC.     

Ultrasonographic changes in malignant neck nodes during radiotherapy in head and neck squamous carcinoma

Limited information is available about the sonomorphological changes in metastatic neck nodes during radiotherapy. The aim of this study was to evaluate the pattern of sonomorphological changes in metastatic neck nodes with radiotherapy. The study population consisted of 16 consecutive patients planned for radical radiotherapy to the head and neck. All patients were subjected to four ultrasound examinations: before therapy, at 46 Gy, at the conclusion of radiation and at first follow up. A total of 59 ultrasound examinations were performed on 16 patients. The difference between the mean number of nodes detected per patient before (10.6) and after (7.8) radiation was significant (P = 0.05). Sixteen nodes were categorized as malignant at first sonography, half of which reverted back to normal by the end of radiation. Changes in the sonomorphology of malignant cervical lymph nodes occur with radiotherapy with more that half demonstrating reversion to normal pattern. Future studies correlating this with histopathology should be considered.     

Diffusion-weighted magnetic resonance imaging of head and neck squamous cell carcinomas

Objective

To evaluate whether diffusion-weighted imaging (DWI) is a reliable technique to quantify microstructural differences between head and neck squamous cell carcinomas (SCC) and tumour-free soft tissue.

Materials and methods

DWI was obtained from 20 patients with histologically proven, untreated head and neck SCC. DWI was acquired using a diffusion-weighted, navigated echo-planar imaging sequence with a maximum b-value of 800 s/mm². For an objective assessment of image quality, the signal-to-noise ratio (SNR) was calculated. Microstructural differences between vital tumour tissue and tumour-free soft tissue were quantified by calculating the apparent-diffusion-coefficients (ADC) on a pixel by pixel method.

Results

Echo-planar DWI provided good image quality in all patients (mean SNR 18.4). The mean ADC of SCC, (0.64 ± 0.28 × 10⁻³ mm²/s), was significantly (P < 0.0001) lower than that of the tumour-free soft tissue, (2.51 ± 0.82 × 10⁻³ mm²/s).

Conclusion

DWI is a reliable diagnostic tool to quantify the microstructural differences between vital tumour tissue and tumour-free soft tissue in patients with head and neck SCC.     

Neutron therapy for locally advanced head and neck squamous cell carcinoma: optimum dose search

28 patients with locally advanced primary squamous cell carcinoma of the head and neck received neutron therapy and were randomized between two dose levels: 145 cGy n gamma x twelve fractions, three fractions per week (total 17.4 Gy n gamma). 155 cGy n gamma x twelve fractions, three fractions per week (total 18.6 Gy n gamma). Acute toxicity for skin, mucous membrane, salivary and subcutaneous tissues was graded using the EORTC/RTOG scoring system. Analysis indicates 17.4 Gy n gamma as "safe". A further twelve patients are to be assigned to the higher dose (18.6 Gy n gamma) before making a final dose selection.     

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma

Objective  

To evaluate the usefulness of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO)-positron emission tomography (PET) prior to the treatment of head and neck squamous cell carcinoma.     

A case of head and neck cutaneous squamous cell carcinoma highlighting aggressive perineural features

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in the United States following basal cell carcinoma. The majority are successfully cured by surgical excision or Mohs microsurgery. A subset of cSCCs are more aggressive and likely to recur locally, spread to regional lymph nodes or even distantly, and can even result in death. High-risk features of cSCC including perineural invasion of nerve >0.1 mm in diameter and invasion beyond the subcutaneous fat are not routinely reported by Mohs microsurgery. Facial cSCC commonly involves branches of the facial nerve (VII) or trigeminal nerve (V). Clinical symptoms associated with cranial nerve VII and V involvement include pain, paresthesia of the face and tongue, facial paralysis. Assessment of nerve involvement by magnetic resonance imaging (MRI) is the most optimal imaging modality. Here, we present a case where Mohs microsurgery was performed on a facial cSCC 1.5 years prior to the development of facial paresis. We aim to highlight the interesting perineural path resulting in facial paralysis and associated symptomatology, the importance of MRI, and to remind clinicians of important high-risk features of cSCC.