Head and neck cancer with synchronous nodules of the lung as a diagnostic and therapeutic challenge - A systematic review.

Head and neck squamous cell carcinoma (HNSCC) often presents with synchronous nodules of the lung (sNL), which may be benign nodules, second primary malignancies or metastases of HNSCC. We sought to gain an insight into the incidence of sNL and synchronous second primary of the lung (sSPML) in HNSCC patients and current opinions on useful diagnostic and therapeutic approaches. We conducted a systematic search of the PubMed database for articles that reported the simultaneous detection of HNSCC and sNL/sPML, within the timeframe of diagnosis and staging. Only studies involving humans were included, without restrictions for sex, age, ethnicity, or smoking history. All articles were categorised according to the Oxford Centre of Evidence-Based Medicine levels and their data collected. Data from 24 studies were analysed. Amongst HNSCC, the mean overall incidence rate of sNL and sSPML was 11.4% (range: 1.3-27%) and 2.95% (range: 0.4-7.4%), respectively. The possibility of a sNL to be a sSPML cannot be ignored (mean: 35.2%). Studies investigating smoking habits showed that the majority (98-100%) of HNSCC patients with sSPML were previous or active smokers. Detection of human papillomavirus through DNA analysis, p16 immunohistochemistry, and identification of clonal evolution were useful in differentiating metastasis from sSPML. 18FDG-PET scan was the most reliable method to diagnose sSPML (sensitivity: 95%; specificity: 96%; positive predictive value: 80%). With early sSPML detection and curative treatment, the 5-year overall survival rate is 34-47%. However, the proposed advantage of early detection warrants further evidence-based justification

Diagnostic accuracy of MRI and PET/CT for neck staging prior to salvage total laryngectomy

Aim: Lymph node (LN) metastases are associated with poor outcomes in patients with recurrent larynx squamous cell carcinoma (LSCC). Neck dissection (ND) is therefore commonly performed along with salvage total laryngectomy (STL). Here, we assess the rate of occult LN metastases and the diagnostic value of MRI and PET/CT for detecting them in recurrent LSCC. Methods: This retrospective study included patients with recurrent LSCC after primary (chemo)radiotherapy [(C)RT] who were re-staged by MRI and/or PET/CT and treated with STL and ND between 2004 and 2019. The histopathology of ND samples was used as the reference standard. Results: Forty-one patients were included. The prevalence of occult metastases in MRI-negative and PET/CT-negative neck nodes was between 3.2% and 6.1%. Negative predictive values of neck node re-staging were 93.9% for MRI, 96.8% for PET/CT, and 96.2% for MRI and PET/CT combined. Conclusion: Both MRI and PET/CT afforded good negative predictive values for nodal staging in patients with recurrent LSCC after (C)RT prior to STL. In selected patients, these radiological modalities, particularly PET/CT, could help to avoid unnecessary surgery to the neck and its associated morbidity

Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial

To test the hypothesis on prolonged survival in glioblastoma cases with increased subventricular zone (SVZ) radiation dose. Sixty glioblastoma cases were previously treated with adjuvant radiotherapy and Temozolamide. Ipsilateral, contralateral and bilateral SVZs were contoured and their doses were retrospectively evaluated. Median follow-up, progression free survival (PFS) and overall survival (OS) were 24.5, 8.5 and 19.3months respectively. Log-rank tests showed a statistically significant correlation between contralateral SVZ (cSVZ) dose >59.2Gy (75th percentile) and poor median PFS (10.37 [95% CI 8.37-13.53] vs 7.1 [95% CI 3.5-8.97] months, p=0.009). cSVZ dose>59.2Gy was associated with poor OS in the subgroup with subtotal resection/biopsy (HR: 4.83 [95% CI 1.71-13.97], p=0.004). High ipsilateral SVZ dose of >62.25Gy (75th percentile) was associated with poor PFS in both subgroups of high performance status (HR: 2.58 [95% CI 1.03-6.05], p=0.044) and SVZ without tumoral contact (HR: 10.57 [95% CI 2.04-49], p=0.008). The effect of high cSVZ dose on PFS lost its statistical significance in multivariate Cox regression analysis. We report contradictory results compared to previous publications. Changing the clinical practice based on retrospective studies which even do not indicate consistent results among each other will be dangerous. We need carefully designed prospective randomized studies to evaluate any impact of radiation to SVZ in glioblastoma

a retrospective analysis

Purpose: We looked for any predictive value of change in primary tumor and metastatic lymph node volumes after induction chemotherapy (IC) on oncologic outcome in head and neck squamous cell carcinoma (HNSCC). Methods: Nineteen patients with stage IVA/B HNSCC treated between 2004 and 2010 with at least one cycle of IC (docetaxel, cisplatin and 5-fluorouracil / TPF) and concomitant chemoradiotherapy (CRT) with cisplatin were retrospectively analyzed. Volumes were calculated separately for primary tumor (Vtm), lymph node metastases (Vln) and their sum (Vsum) on computed tomography (CT) images before and after IC. The effect of volumetric changes on locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) was assessed. P values <0.05 were considered as statistically significant. Results: The median follow-up of surviving patients was 25 months (range: 10.7-83.3). The median number of cycles and duration of TPF was 3 (range: 1-4) and 44 days (range: 4-116), respectively. Empirical area under the curve (AUC) analyses for death, LRF and DM revealed optimal cut-off values of Vtm diminution (30.54%, AUC: 87%) and Vsum decrease (35.45%, AUC: 64.55%) only for OS (p <0.05). Among those, a reduction in Vsum more than 35.4% between pre- and post-IC was significantly correlated with better OS (100 vs 43% at 2 years, p <0.05). Conclusion: Volumetric shrinkage of the tumor load after IC assessed with CT seems to predict OS. The assessment of volumetric shrinkage upon IC might be used to decide whether to offer patients alternative strategies like palliative/de-intensified treatments or more aggressive combined modalities after IC

Reirradiation of head and neck squamous cell carcinomas: a pragmatic approach-part I: prognostic factors and indications to treatment.

INTRODUCTION Reirradiation (reRT) of locally recurrent/second primary tumors of the head and neck region is a potentially curative treatment for patients not candidate to salvage surgery. Aim of the present study is to summarize available literature on both prognostic factors and indications to curative reRT in this clinical setting. MATERIALS AND METHODS A narrative review of the literature was performed on two topics: (1) patients' selection according to prognostic factors and (2) dosimetric feasibility of reRT. Postoperative reRT and palliative intent treatments were out of the scope of this work. RESULTS Patient-tumor and treatment-related prognostic factors were analyzed, together with dosimetric parameters concerning target volume and organs at risk. Based on available evidence, a stepwise approach has been proposed aiming to provide a useful tool to identify suitable candidates for curative reRT in clinical practice. This was then applied to two clinical cases, proposed at the end of this work. CONCLUSION A second course of RT in head and neck recurrence/second primary tumors is a personalized approach that can be offered to selected patients only in centers with expertise and dedicated equipment following a multidisciplinary team discussion

Organ-at-risk sparing with dynamic trajectory radiotherapy for head and neck cancer: comparison with volumetric arc therapy on a publicly available library of cases.

BACKGROUND Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation during beam-on. The aim of the study is to establish DTRT path-finding strategies, demonstrate deliverability and dosimetric accuracy and compare DTRT to state-of-the-art VMAT for common head and neck (HN) cancer cases. METHODS A publicly available library of seven HN cases was created on an anthropomorphic phantom with all relevant organs-at-risk (OARs) delineated. DTRT plans were generated with beam incidences minimizing fractional target/OAR volume overlap and compared to VMAT. Deliverability and dosimetric validation was carried out on the phantom. RESULTS DTRT and VMAT had similar target coverage. For three locoregionally advanced oropharyngeal carcinomas and one adenoid cystic carcinoma, mean dose to the contralateral salivary glands, pharynx and oral cavity was reduced by 2.5, 1.7 and 3.1 Gy respectively on average with DTRT compared to VMAT. For a locally recurrent nasopharyngeal carcinoma, D0.03 cc to the ipsilateral optic nerve was above tolerance (54.0 Gy) for VMAT (54.8 Gy) but within tolerance for DTRT (53.3 Gy). For a laryngeal carcinoma, DTRT resulted in higher dose than VMAT to the pharynx and brachial plexus but lower dose to the upper oesophagus, thyroid gland and contralateral carotid artery. For a single vocal cord irradiation case, DTRT spared most OARs better than VMAT. All plans were delivered successfully on the phantom and dosimetric validation resulted in gamma passing rates of 93.9% and 95.8% (2%/2 mm criteria, 10% dose threshold). CONCLUSIONS This study provides a proof of principle of DTRT for common HN cases with plans that were deliverable on a C-arm linac with high accuracy. The comparison with VMAT indicates substantial OAR sparing could be achieved

Role of fluorine-18 fluorodeoxyglucose PET/CT in head and neck oncology: the point of view of the radiation oncologist

Squamous cell carcinoma is the most common malignant tumour of the head and neck. The initial TNM staging, the evaluation of the tumour response during treatment, and the long-term surveillance are crucial moments in the approach to head and neck squamous cell carcinoma (HNSCC). Thus, at each of these moments, the choice of the best diagnostic tool providing the more precise and larger information is crucial. Positron emission tomography with fluorine-18 fludeoxyglucose integrated with CT (F-18-FDG-PET/CT) rapidly gained clinical acceptance, and it has become an important imaging tool in routine clinical oncology. However, controversial data are currently available, for example, on the role of F-18-FDG-PET/CT imaging during radiotherapy planning, the prognostic value or its real clinical impact on treatment decisions. In this article, the role of F-18-FDG-PET/CT imaging in HNSCC during pre-treatment staging, radiotherapy planning, treatment response assessment, prognosis and follow-up is reviewed focusing on current evidence and controversial issues. A proposal on how to integrate F-18-FDG-PET/CT in daily clinical practice is also described

Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer—A Multicenter Study

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy. Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models. Results: The median follow-up was 63 months (range: 2-243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47-11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08-2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38-2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44-11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01-2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses. Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome

Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed