Image findings of cranial nerve pathology on [18F]-2- deoxy-D-glucose (FDG) positron emission tomography with computerized tomography (PET/CT): a pictorial essay.

This article aims to increase awareness about the utility of (18)F -FDG-PET/CT in the evaluation of cranial nerve (CN) pathology. We discuss the clinical implication of detecting perineural tumor spread, emphasize the primary and secondary (18)F -FDG-PET/CT findings of CN pathology, and illustrate the individual (18)F -FDG-PET/CT CN anatomy and pathology of 11 of the 12 CNs

Patients with head and neck cancer - aspects on treatment, complications and rehabilitation

Head and neck cancer is reported to be the fifth most common cancer globally and around 1,200 new patients are diagnosed in Sweden every year. Historically, survival rates have been rather constant but have started to improve over the last few decades as a result of new and more aggressive oncological treatments. For this reason, there is a need to re-evaluate surgical treatment—both its necessity and its morbidity in comparison to the oncological treatments available. There is also a risk of higher incidence of side effects from newer oncological regimens, which still needs to be evaluated. In this thesis, different populations of head and neck cancer patients from our institution have been analysed concerning aspects of treatment, sequelae, and rehabilitation. The material is highly applicable to everyday clinical situations. In paper I, patients diagnosed between1998 and 2002 with metastases in the neck that were treated with full-dose external beam radiotherapy (EBRT) were evaluated concerning histopathology and clinical outcome, with a view to evaluating the necessity of a planned neck dissection after EBRT. One hundred and fifty-six patients were included. Overall survival was 62% and disease-specific survival was 76%. There was a clinically complete response to radiotherapy in the neck in 63 patients (40%). Of these, 15 had viable tumor cells in the neck specimen. In patients who did not achieve a clinically complete response, 40% (37/93) had viable tumor cells in the neck specimen. Disease-specific survival in patients with viable tumor cells in the neck after EBRT was 48% (25/52), and it was 90% (93/104) in patients without viable tumor cells. Paper II describes a retrospective case-control study of patients diagnosed and treated for stricture of the upper oesophagus after EBRT for head and neck cancer between 1992 and 2005. The aim of the study was to identify possible risk factors for stricture formation. Clinical parameters were collected from the medical files. The EBRT dose delivered to the upper oesophagus was calculated using the dose-planning system data. Seventy patients with stricture and 66 patients without were identified. The incidence of upper esophageal stricture at the institution during the study period was 3.3%. A multivariate analysis showed an increased risk of stricture in patients who received enteral feeding during EBRT or with a mean dose of > 45 Gy delivered to the upper oesophagus. Treatment of the stricture with Savary-Gilliard bougienage or through-thescope balloon dilatation was found to be safe and successful, but often had to be repeated. In paper III, the morbidity of supraomohyoidal neck dissection (SOND) or modified radical neck dissection (MRND) combined with EBRT was evaluated regarding cervical range of movement, lymphoedema, mouth opening, swallowing, and shoulder disability. The patient material was collected from the study population in paper IV. Ninety-eight patients who received only EBRT were identified, 25 patients were treated with both SOND and EBRT, and 83 were treated with MRND and EBRT. The overall incidence of shoulder disability after both types of neck dissection was 18%. SOND had no other significant negative effects on the parameters under evaluation at any time 5 point, while with MRND there was significantly reduced CROM and mouth opening two months after treatment. After 12 months, only cervical rotation was still significantly reduced. In paper IV, the aim of the study was to evaluate the effect of an early preventive rehabilitation programme on functional losses and quality of life. The programme started at diagnosis before the start of treatment and was based on self-care after receiving instructions from a speech language pathologist and a physiotherapist. The patients were instructed to use the training programme during and after the treatment period. One hundred and ninety patients were included in the early experimental rehabilitation programme. A control group of 184 patients who did not receive early rehabilitation was constructed. It was shown that the programme could be implemented without delaying the start of oncological treatment, but no positive effects concerning survival, weight loss, functional loss, working ability, or quality of life were observed. The need for a neck dissection after EBRT cannot be determined by clinical examination as a high percentage of patients with clinical complete response showed viable tumor cells in the neck specimen. When performing a neck dissection, a SOND should be considered in suitable patients as morbidity of SOND is low except for shoulder disability. An EBRT dose delivered to the upper 5 cm of the oesophagus should be kept below 45 Gy to lower the risk of oesophageal stricture, and patients should be instructed to continue to swallow even if they receive enteral nutrition during treatment. Finally, even though no positive effects of early rehabilitation could be shown, the results do not contradict the idea that rehabilitation based on self-care can be effective. Efforts should be made to identify rehabilitation that can reduce functional losses and improve quality of life. Future rehabilitation programmes should also concentrate on identification of proper instruments for selection of patients and for evaluation of intervention in head and neck cancer patients

Characterizing Risk & Burden Of Lower Cranial Neuropathy (Lcnp) As Late Effect Among Oropharyngeal Cancer Survivors

Background: Lower cranial neuropathy (LCNP) is a rare but potentially disabling late effect of radiotherapy (RT) and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment with deficits in swallowing, speech, and voice. The aims of this research were: 1) to quantify the cumulative incidence of late LCNP and identify clinical predictors of late LCNP; 2) to investigate the impact of late LCNP on severity of cancer treatment-related symptoms, general functional impairment (GFI), and single item scores of the most severe symptoms; and 3) to quantify the association of late LCNP with swallowing-related quality of life (QoL) and functional status among long-term oropharyngeal cancer (OPC) survivors. Methods: For the first aim of this dissertation the study population included 2,021 OPC survivors (median survival: 6.8 years) who received primary treatment at MD Anderson Cancer Center from 2000 to 2013. A retrospective cohort study was conducted and late LCNP events for all three studies were defined by neuropathy of the glossopharyngeal (IX), vagus (X), and/or hypoglossal (XII) nerves ≥3-months after cancer therapy and abstracted from medical records along with other study variables. For the second and third study, a cross-sectional survey analysis among 889 OPC survivors nested within a retrospective cohort of OPC survivors treated during January 2000 -December 2013 at MD Anderson Cancer Center was conducted (56% response rate). The survey included MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN) and MD Anderson Dysphagia Inventory (MDADI) among other items. For the first study, cumulative incidence of LCNP was estimated using the Kaplan Meir method with adjustment for competing risks using time to event as the underlying metric. Log-rank test was used to assess differences between groups by LCNP status, and multivariable Cox proportional hazard models were fit. For the second study, the primary outcome variable was the mean of the top 5 most severely scored symptoms from MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN) out of all 22 core and HNC-specific symptoms. Secondary outcomes included mean MDASI-HN interference scores and single item scores of the most severe symptoms. Multivariate models regressed MDASI-HN scores on late LCNP status adjusting for clinical covariates. Finally, for the third study, multivariate models regressed MDADI scores on late LCNP status adjusting for clinical covariates. Results: For the first study; 4.4% (n=88) OPC survivors were diagnosed with late LCNP with median time to LCNP onset after treatment of 5.4 (range, 0.3-14.1; IQR: 1.6-8.5) years post-treatment. Cumulative incidence of LCNP among all OPC survivors was 0.02 (95% CI: 0.02-0.03), 0.06 (95% CI: 0.05-0.08), and 0.10 (95% CI: 0.08-0.13) at 5 years, 10 years, and 18 years of follow-up, respectively. Multivariable Cox regression identified T4 stage vs T1 stage (HR: 3.82; 95%CI: 1.85-7.86, p=0.000) and accelerated RT fractionation vs standard RT fractionation (HR 2.15, 95%CI 1.34-3.45, p=0.002) independently associated with late LCNP status, adjusting for age, subsite, T-stage, smoking and therapeutic modality. In the second and third, cross-sectional survey analysis study overall, 4% (n=36) of 889 OPC survivors (median survival time: 7 years) developed late LCNP with median time to onset of 5.25 years post-treatment. Late LCNP was significantly associated with worse mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95%CI, 0.8, 2.2) adjusting for age, survival time, sex, therapeutic modality, T-stage, subsite, type of radiotherapy, smoking, and normal diet prior to treatment. Late LCNP was also associated with single item scores for difficulty swallowing/chewing (coefficient, 2.25; 95%CI, 1.3, 3.1), mucus (coefficient, 1.97; 95%CI, 1.0, 2.9), fatigue (coefficient, 1.35; 95%CI, 0.4, 2.2), choking (coefficient, 1.53; 95%CI, 0.6, 2.4), and voice/ speech symptoms (coefficient, 2.3; 95%CI, 1.6, 3.0) in multivariable models. However late LCNP was not significantly associated with mean interference scores after correction for multiple comparisons. LCNP cases reported significantly worse mean composite MDADI (LCNP: 68.0 vs. no LCNP: 80.2, p\u3c0.001). Late LCNP independently associated with worse mean composite MDADI (β= -6.7, p=0.015, 95%CI: -12.0, -1.3) as well as all MDADI domains after multivariate adjustment. Finally, LCNP cases were more likely to have a feeding tube at time of survey (OR= 20.5; 95%CI, 8.6 to 48.9), history of aspiration pneumonia (OR= 23.5; 95%CI, 9.6 to 57.6), and tracheostomy (OR= 26.9; 95%CI, 6.0 to 121.7). Conclusion: Risk of late LCNP progressed over time to exceed 10% cumulative risk over survivors’ lifetime even though it is considered a rare late effect. Our prediction model enabled identification of OPC survivors who had T4 tumors and those who received accelerated fractionation RT treatment as having higher risk of late LCNP. In the large survey study, OPC survivors with late LCNP reported significantly worse cancer treatment related symptoms, significantly poorer swallowing-related QOL and had significantly higher likelihood of poor functional status demonstrating the impact of late LCNP on both symptom severity and functional burden. Further, efforts are necessary to investigate the risk and predictors for this disabling late effect of cancer treatment, address severity of treatment related symptoms and optimize swallowing outcomes to improve QoL among growing numbers of relatively younger OPC survivors, who are expected to survive decades after treatment

Intensity modulated radiation therapy and arc therapy: validation and evolution as applied to tumours of the head and neck, abdominal and pelvic regions

Intensiteitsgemoduleerde radiotherapie (IMRT) laat een betere controle over de dosisdistributie (DD) toe dan meer conventionele bestralingstechnieken. Zo is het met IMRT mogelijk om concave DDs te bereiken en om de risico-organen conformeel uit te sparen. IMRT werd in het UZG klinisch toegepast voor een hele waaier van tumorlocalisaties. De toepassing van IMRT voor de bestraling van hoofd- en halstumoren (HHT) vormt het onderwerp van het eerste deel van deze thesis. De planningsstrategie voor herbestralingen en bestraling van HHT, uitgaande van de keel en de mondholte wordt beschreven, evenals de eerste klinische resultaten hiervan. IMRT voor tumoren van de neus(bij)holten leidt tot minstens even goede lokale controle (LC) en overleving als conventionele bestralingstechnieken, en dit zonder stralingsgeïnduceerde blindheid. IMRT leidt dus tot een gunstiger toxiciteitprofiel maar heeft nog geen bewijs kunnen leveren van een gunstig effect op LC of overleving. De meeste hervallen van HHT worden gezien in het gebied dat tot een hoge dosis bestraald werd, wat erop wijst dat deze “hoge dosis” niet volstaat om alle clonogene tumorcellen uit te schakelen. We startten een studie op, om de mogelijkheid van dosisescalatie op geleide van biologische beeldvorming uit te testen. Naast de toepassing en klinische validatie van IMRT bestond het werk in het kader van deze thesis ook uit de ontwikkeling en het klinisch opstarten van intensiteitgemoduleerde arc therapie (IMAT). IMAT is een rotationele vorm van IMRT (d.w.z. de gantry draait rond tijdens de bestraling), waarbij de modulatie van de intensiteit bereikt wordt door overlappende arcs. IMAT heeft enkele duidelijke voordelen ten opzichte van IMRT in bepaalde situaties. Als het doelvolume concaaf rond een risico-orgaan ligt met een grote diameter, biedt IMAT eigenlijk een oneindig aantal bundelrichtingen aan. Een planningsstrategie voor IMAT werd ontwikkeld, en type-oplossingen voor totaal abdominale bestraling en rectumbestraling werden onderzocht en klinisch toegepast

Risk and Clinical Risk Factors associated With Late Lower Cranial Neuropathy in Long-Term oropharyngeal Squamous Cell Carcinoma Survivors

IMPORTANCE: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors). OBJECTIVE: to estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors. DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, 2013. Exclusion criteria consisted of baseline LCNP, recurrent head and neck cancer, treatment at other institutions, death, and a second primary, persistent, or recurrent malignant neoplasm of the head and neck less than 3 months after treatment. Median survival of OPSCC among the 2021 eligible patients was 6.8 (range, 0.3-18.4) years. Data were analyzed from October 12, 2019, to November 13, 2020. MAIN OUTCOMES AND MEASURES: Late LCNP events were defined by neuropathy of the glossopharyngeal, vagus, and/or hypoglossal cranial nerves at least 3 months after cancer therapy. Cumulative incidence of LCNP was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were fit. RESULTS: Among the 2021 OPSCC survivors included in the analysis of this cohort study (1740 [86.1%] male; median age, 56 [range, 28-86] years), 88 (4.4%) were diagnosed with late LCNP, with median time to LCNP of 5.4 (range, 0.3-14.1) years after treatment. Cumulative incidence of LCNP was 0.024 (95% CI, 0.017-0.032) at 5 years, 0.061 (95% CI, 0.048-0.078) at 10 years, and 0.098 (95% CI, 0.075-0.128) at 15 years of follow-up. Multivariable Cox proportional hazards regression identified T4 vs T1 classification (hazard ratio [HR], 3.82; 95% CI, 1.85-7.86) and accelerated vs standard radiotherapy fractionation (HR, 2.15; 95% CI, 1.34-3.45) as independently associated with late LCNP status, after adjustment. Among the subgroup of 1986 patients with nonsurgical treatment, induction chemotherapy regimens including combined docetaxel, cisplatin, and fluorouracil (TPF) (HR, 2.51; 95% CI, 1.35-4.67) and TPF with cetuximab (HR, 5.80; 95% CI, 1.74-19.35) along with T classification and accelerated radiotherapy fractionation were associated with late LCNP status after adjustment. CONCLUSIONS AND RELEVANCE: This single-institution cohort study found that, although rare in the population overall, cumulative risk of late LCNP progressed to 10% during the survivors\u27 lifetime. As expected, clinical factors associated with LCNP primarily reflected greater tumor burden and treatment intensity. Further efforts are necessary to investigate risk-reduction strategies as well as surveillance and management strategies for this disabling late effect of cancer treatment

Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed