Pattern of dysphagia after swallowing-sparing intensity-modulated radiotherapy (IMRT) of head and neck cancers: results of a mono-institutional prospective study.

BACKGROUND AND PURPOSE: A prospective instrumental assessment of late dysphagia using swallowing organs at risk (SWOARs)-sparing IMRT for nasopharyngeal and oropharyngeal cancers. MATERIALS AND METHODS: Objective instrumental assessment included fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy (VFS) at baseline, and at 6 and 12 months after treatment. FEES assessed the pharyngeal residue according to the Farneti pooling score (P-score) as follows: 4-5 no dysphagia; 6-7 mild dysphagia; 8-9 moderate dysphagia; 10-11 severe dysphagia. Three different consistencies were tested for the P­score: liquid (L), semisolid (SS), and solid (S). VFS assessed penetration-aspiration according to the Penetration-Aspiration Scale (PAS) and two different consistencies of the bolus were tested: thin liquid barium (L) and paste barium (S). RESULTS: 38 patients were evaluable. There was a significant worsening of the P­score at 6 months both for SS (p = 0.015) and S (p < 0.001), which persisted only for S at 12 months (p < 0.0001). Similarly, there was a significant worsening of the PAS score at 6 and 12 months (p = 0.065 and 0.039, respectively) for the S bolus. Overall, 3-7 and 10-14% aspiration after L and S was observed, respectively. CONCLUSIONS: Promising results using a SWOARs-sparing IMRT technique are reported. Therefore, treatment plans should be optimized for reducing doses to these structures.

A comparison of swallowing dysfunction after three-dimensional conformal and intensity-modulated radiotherapy : A systematic review by the Italian Head and Neck Radiotherapy Study Group.

PURPOSE: Dysphagia is one of the most important treatment-related side effects in head and neck cancer (HNC), as it can lead to severe life-threating complications such as aspiration pneumonia and malnutrition. Intensity-modulated radiotherapy (IMRT) could reduce swallowing dysfunction by producing a concave dose distribution and reducing doses to the swallowing-related organs at risk (SWOARs). The aim of this study was to review the current literature in order to compare swallowing outcomes between IMRT and three-dimensional conformal radiotherapy (3DCRT). METHODS: A search was conducted in the PubMed and Embase databases to identify studies on swallowing outcomes, both clinically and/or instrumentally assessed, after 3DCRT and IMRT. Dysphagia-specific quality of life and objective instrumental data are summarized and discussed. RESULTS: A total of 262 papers were retrieved from the searched databases. An additional 23 papers were retrieved by hand-searching the reference lists. Ultimately, 22 papers were identified which discussed swallowing outcomes after 3DCRT and IMRT for HNC. No outcomes from randomized trials were identified. CONCLUSION: Despite several methodological limitations, reports from the current literature seem to suggest better swallowing outcomes with IMRT compared to 3DCRT. Further improvements are likely to result from the increased use of IMRT plans optimized for SWOAR sparing.

Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience.

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12-109 months). At 5 years, in-field LC was 99.2% (95% CI: 98-99.7); out-field LC 98.9% (95% CI: 97.4-99.6); DFS 96.2% (95% CI: 94.2-97.6); OS 98.6% (95% CI: 97.2-99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Systemic therapy augmented by radiotherapy (STAR) effect for brain metastases in a BRAF-mutated melanoma patient with prolonged survival: a case report.

Brain metastases are common in stage IV malignant melanoma, carrying a prognosis traditionally regarded as severe, with a median survival of few months. Recently introduced systemic therapies as targeted therapy or immunotherapy have significantly improved the prognosis of metastatic melanoma. The optimal association of radiotherapy to such novel treatments has to be clarified. We report on a 43-year-old woman with 10 brain metastases. Three of them were treated with stereotactic radiosurgery (SRS) with complete response even of the untreated lesions. As the patient was BRAF-mutated, she was started on dabrafenib/trametinib. After 8 months she developed new brain metastases, which again responded to a new treatment with SRS. As after 7 months additional lesions appeared, she was treated with whole brain radiotherapy and was started on nivolumab. Twenty months after the first diagnosis of brain metastases the patient is fit without significant clinical and radiological signs of toxicity.

The Relevance of Assessing Subjective Experiences of Skin Toxicity During Adjuvant Radiotherapy for Breast Cancer.

PURPOSE: Radiodermatitis is likely to be an inevitable side effect of radiotherapy (RT) but experiencing pain relief during RT might contribute making treatment more acceptable and less impairing. The current study aimed to assess the subjective perceptions and experiences of skin toxicity in a sample of women undergoing adjuvant RT for breast cancer. METHODS: Eighty patients were randomly assigned to one out of two groups: treatment (i.e., a newly developed topical product) and control (i.e., standard-of-care). Patients underwent adjuvant RT for 3 weeks. Clinical assessment of radiodermatitis and self-reported levels of pain, relief, and perceptions of treatment response were collected at the initiation of RT (T1), during RT (T2 and T3), and 2 weeks after treatment completion (T4). To assess changes in skin-related QoL, a subgroup of patients completed the Padua Skin-Related QoL questionnaire at T0 (before the initiation of RT) and at T4. RESULTS: A comparable timing of onset and severity of radiodermatitis during treatment was observed in both groups. The treatment group reported lower levels of pain and higher levels of relief compared to the control group when skin toxicity was at its highest levels (T2 and T3). Independent of the group, levels of perceived improvements in clinical status increased over time, whereas skin-related QoL worsened from T0 to T4. CONCLUSION: Current findings outline the relevance of integrating clinical evaluations of radiodermatitis with patients' subjective experiences of skin toxicity in interventional studies. Moreover, they provide preliminary evidence about the soothing effect of a newly developed topical product, thus supporting its usefulness of as a supportive care.

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature.

BACKGROUND: The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIM: To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODS: In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors' searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTS: The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSION: Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.

Squamous cell carcinoma (SCC) of the Pyriform sinus with multiple metachronous brain metastases, a case report.

BACKGROUND: Distant Metastases from Head and Neck Squamous cell carcinomas are uncommon (9-11%) and they are usually found in the lung and less frequently in the liver, kidney and adrenals. Central nervous system (CNS) metastases are extremely rare (2-8%), and they are described mainly in patients who already have extracranial metastases. So there's scarcity of data about their optimal management . METHODS AND RESULTS: A patient presented CNS metastases after having been successfully treated with induction chemotherapy and definitive radiotherapy for a pyriform sinus carcinoma. The patient's work up, treatment and outcome are described. CONCLUSIONS: CNS metastases from Head and Neck carcinomas are exceptionally rare. Nevertheless, clinicians should be alert of neurological symptoms in these patients, in order to set up a timely assessment and treatment. Secondarily, given the rarity of this condition, additional research on this topic is warranted in order to improve therapeutic strategies and outcomes of such patients.

Radiation-induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? "A narrative review".

Radiation therapy is one of the cornerstones in the treatment of head and neck squamous cell carcinomas (HNSCC), alone or in combination with chemotherapy or surgery. Technological advances which occurred over the last few decades have increased the efficacy of radiotherapy (RT), particularly, intensity-modulated RT (IMRT). IMRT can deliver treatments on complex tumoral targets with dose escalation while sparing organs at risk; anyway IMRT deposits dose in unpredictable patterns outside of the target volume with the purpose of improving conformality. Radiation-induced nausea and vomiting (RINV) is a frequent albeit neglected side effect of RT that can lead to delays in treatment with serious consequences on cure rates. According to several guidelines (MASCC 2016, NCCN 2018), RT for HNSCC has traditionally been regarded as a low emetic risk treatment. Nevertheless, several works suggest that IMRT could increase RINV. Further studies are needed to define the exact incidence and the detailed pathophysiology of RINV in patients with HNSCC treated with state of art IMRT techniques, with and without concurrent chemotherapy.

Assessing Novel Drugs and Radiation Technology in the Chemoradiation of Oropharyngeal Cancer.

Integrating immunotherapy, proton therapy and biological dose escalation into the definitive chemoradiation of oropharyngeal cancer poses several challenges. Reliable and reproducible data must be obtained in a timely fashion. However, despite recent international radiotherapy contouring guidelines, controversy persists as to the applicability of such guidelines to all cases. Similarly, a lack of consensus exists concerning both the definition of the organ at risk for oral mucositis and the most appropriate endpoint to measure for this critical toxicity. Finally, the correlation between early markers of efficacy such as complete response on PET CT following treatment and subsequent survival needs elucidation for biological subsets of oropharyngeal cancer.

Set-up errors in head and neck cancer treated with IMRT technique assessed by cone-beam computed tomography: a feasible protocol.

PURPOSE: To investigate set-up errors, suggest the adequate planning target volume (PTV) margin and image-guided radiotherapy frequency in head and neck (H&N) cancer treated with intensity-modulated radiotherapy (IMRT) assessed by kV cone-beam computed tomography (CBCT). METHODS: We analyzed 360 CBCTs in 60 patients with H&N cancer treated with IMRT. The target delineation was contoured according to ICRU62. PTVs were generated by adding a 3-5 mm margin in all directions to the respective clinical target volumes. The kV CBCT images were obtained at first three days of irradiation and weekly thereafter. The overall mean displacement, range, systematic (∑) and random (σ) errors were calculated. Adequate PTV margins were calculated according to the van Herk formula (2.5∑ + 0.7r). RESULTS: The mean of set-up errors was less than 2 mm in any direction. The overall frequency of set-up displacements greater than 3 mm was 3.9% in medial-lateral (ML) direction, 8% in superior-inferior (SI) direction, and 15.5% in anterior-posterior (AP) direction. The range of translations shifts was 0-9 mm in ML direction, 0-5 mm in SI direction and 0-10 mm in AP direction, respectively. After systematic set-up errors correction, the adequate margin to overcome the problem of set-up errors was found to be less than 3 mm. CONCLUSION: Image-guided kV CBCT was effective for the evaluation of set-up accuracy in H&N cancer. The kV CBCT at first three fractions and followed-by weekly appears adequate for reducing significantly set-up errors in H&N cancer treated with IMRT technique. Finally, 3-5 mm PTV margins appear adequate and safe to overcome the problem of set-up errors.

Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early Versus Delayed Administration.

BACKGROUND/AIM: In patients with recurrent glioblastoma, the best timing to administer bevacizumab is not well addressed yet. In this study, we reported the results of a monocentric experience comparing the early use of bevacizumab (following the first GBM recurrence) with the delayed administration (following the second or even further GBM recurrences). MATERIALS AND METHODS: This analysis included 129 glioblastoma patients with a median follow-up of 22.4 months (range=5.26-192 months). RESULTS: The median time lapse from diagnosis of glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated with deferred administration of bevacizumab and 9.9 for patients with early administration (p=0.047). Bevacizumab progression-free survival with early and delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from the start of bevacizumab was 6.18 months in patients with early administration, and 6.47 in the delayed administration one (p=0.318). CONCLUSION: Delayed administration of bevacizumab can be considered in selected patients with less aggressive recurrent glioblastoma.

Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature.

Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords "radiation necrosis", "radiotherapy" and "bevacizumab" alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy.