Objectives
Swallowing and voice dysfunctions are common side effects following head-and-neck squamous-cell carcinoma (HNSCC) treatment. Our aim was to analyze the relationships between quality of ...life, swallowing, and phonatory problems in patients with an advanced-stage HNSCC and to prospectively evaluate the effects of a prophylactic swallowing program.
Methods
First, we retrospectively studied 60 advanced HNSCC patients treated with exclusive or adjuvant radiotherapy/chemoradiotherapy (RT/CRT). Subjects were classified according to general and clinical–therapeutic features. Outcome measures included EORTC QLQ-C30, EORTC QLQ-H&N35, Dysphagia Handicap Index (DHI), M.D.Anderson Dysphagia Inventory (MDADI), and Voice Handicap Index (VHI). Then, we conducted a prospective evaluation of a prophylactic swallowing counselling in 12 consecutive advanced-stage HNSCC patients by a two-arm case–control analysis. These patients were treated with exclusive or adjuvant RT/CRT.
Results
71% of the retrospective population studied reported swallowing dysfunction as a major side effect. No differences were detected in the severity of dysphagia or dysphonia according to type of treatment or staging of the primary tumour, while hypopharyngeal and laryngeal cancer patients showed significantly better swallowing ability and better QoL compared to oral cavity and oropharyngeal localisation (
p
< 0.05). In addition, a relevant correlation between swallowing and voice problems emerged (
p
< 0.05). In the prospective part, while no statistical correlation was evident before the start of RT/CRT in the experimental group compared to the control one, the former showed better performances at MDADI (
p
= 0.006) and DHI (
p
= 0.002) test 3 months after its end.
Conclusion
Dysphagia is both an acute-and-long-term side effect which greatly affects QoL of HNSCC patients undergoing multimodality treatment. Our data show that a prophylactic swallowing program could actually produce a beneficial effect on patients’ outcomes.
Level of evidence
1b and 2b.
Highlights • Oral mucositis is a complication of radiotherapy used for head-neck cancer treatment. • Rosiglitazone protects normal tissues from radiation-induced oral mucositis. • Rosiglitazone does ...not protect the tumor from therapeutic effect of irradiation. • Rosiglitazone could be proposed as radioprotective agent in head-neck cancer.
•The treatment of elderly patients with head and neck cancer is challenging.•Hypofractionated radiotherapy provides clinical benefit in frail, elderly patients.•A PTV larger than 200 cc is an ...unfavorable prognosticator of response.
The aim of our work was to report on the clinical outcome of a moderately hyprofractionated radiotherapy regimen in elderly patients affected by head and neck squamous cell carcinoma (HNSCC).
HNSCC aged ≥65 deemed unsuitable for curatively-intended concurrent chemo-radiotherapy or high-dose radiotherapy by clinical judgement were further evaluated with the Geriatric 8 (G8) questionnaire and Charlson comorbidity index (CCI). In case of a G8 score ≤14, a de-intensified radiation schedule of 40 Gy delivered in 16 fractions was prescribed.
Thirty-six patients were treated between 2011 and 2016. The median age of the cohort was 77.5 (range: 65–91 years) with a combined ECOG PS of 2–3 in 77.8% and CCI of ≥8 in 25% patients, respectively. At a median follow-up of 13 months (range 2–62 months), the 6-month and 1-year rates of loco-regional control and progression-free survival were 42%, 28% and 36% and 20%, respectively. At univariate analysis, log-rank test showed that age >75 years (p=0.036), worse PS (ECOG≥2; p=0.027), lower G8 score (<9; p=0.027) and PTV volume greater than 200 cc (p=0.038) had a significant correlation with PFS. The negative impact of the PTV volume on PFS was the only parameter confirmed in the multivariate analysis (HR 2.68; 95% CI: 1.24–5.81, p=0.013). No grade 4–5 toxicity was observed, while 13/36 patients (36%) had G3 acute side effects.
The hypofractionated radiation schedule evaluated provides clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC.
•Utility of ctDNA analysis by Next Generation Sequencing in patients with NSCLC.•Driver druggable variants were detected in patients at diagnosis and at progression.•Liquid biopsy allows detection of ...tumour heterogeneity in NSCLC patients.
The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients.
Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score.
A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions.
The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA.
Purpose
Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A ...growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy.
Methods and materials
Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions.
Results
All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60–80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3–58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months,
p
= 0.03 and 22.7 vs. 27 months,
p
= 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months,
p
= 0.02 and 33.5 vs. 53.1 months,
p
= 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5–10.6,
p
= 0.007). No grade > /2 adverse were recorded.
Conclusions
After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, Cyberknife
R
rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa.
Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve ...relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1-G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario.
To determine dose constraints that correlate with alopecia in patients treated with photon-based Volumetric Modulated Arc Therapy (VMAT) for primary brain tumors.
During the treatment planning ...process, the scalp was drawn as a region of interest. Dose received by 0.1 cc (D
), mean dose (D
), absolute volumes receiving different doses (V
, V
, V
, V
, V
, V
, and V
) were registered for the scalp. Alopecia was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Receiver operating characteristics (ROC) curve analysis was used to identify parameters associated with hair-loss.
One-hundred and one patients were included in this observational study. At the end of radiotherapy (RT), 5 patients did not develop alopecia (D
scalp 3.1 Gy). The scalp of the patients with G1 (
= 11) and G2 (
= 85) alopecia received D
of 10.6 Gy and 11.8 Gy, respectively. At ROC analysis, V
≥ 5.2 cc were the strongest predictors of acute alopecia risk. Chronic hair-loss assessment was available for 74 patients: median time to recovery from G2 alopecia was 5, 9 months. The actuarial rate of hair regrowth was 98.1% at 18 months after the end of RT. At ROC analysis, V
≥2.2 cc were the strongest predictors of chronic G2-alopecia risk. V
, V
, and D
were shown to be independent variables according to correlation coefficient r.
V
and V
were the strongest predictors for acute and chronic G2 hair-loss, respectively. The low-dose bath typical of VMAT corresponds to large areas of acute but transient alopecia. However, the steep dose gradient of VMAT allows to reduce the areas of the scalp that receive higher doses, minimizing the risk of permanent alopecia. The application of our dosimetric findings for the scalp may help in reducing the alopecia risk and also in estimating the probability of hair-loss during patient counseling before starting radiotherapy.
•Prostate cancer management should be changed in COVID-19 pandemic.•A practical document was developed in according to recommendations of EAU.•The challenge is reducing risk of virus spreading ...without worsening tumor prognosis.
To adapt the management of prostate malignancy in response to the COVID-19 pandemic.
In according to the recommendations of the European Association of Urology, we have developed practical additional document on the treatment of prostate cancer.
Low-Risk Group Watchful Waiting should be offered to patients >75 years old, with a limited life expectancy and unfit for local treatment. In Active Surveillance (AS) patients re-biopsy, PSA evaluation and visits should be deferred for up to 6 months, preferring non-invasive multiparametric-MRI. The active treatment should be delayed for 6–12 months. Intermediate-Risk Group AS should be offered in favorable-risk patients. Short-course neoadjuvant androgen deprivation therapy (ADT) combined with ultra-hypo-fractionation radiotherapy should be used in unfavorable-risk patients. High-Risk Group Neoadjuvant ADT combined with moderate hypofractionation should be preferred. Whole-pelvis irradiation should be offered to patients with positive lymph nodes in locally advanced setting. ADT should be initiated if PSA doubling time is < 12 months in radio-recurrent patients, as well as in low priority/low volume of metastatic hormone sensitive prostate cancer. If radiotherapy cannot be delayed, hypo-fractionated regimens should be preferred. In high priority class metastatic disease, treatment with androgen receptor-targeted agents should be offered. When palliative radiotherapy for painful bone metastasis is required, single fraction of 8 Gy should be offered.
In Covid-19 Era, the challenge should concern a correct management of the oncologic patient, reducing the risk of spreading the virus without worsening tumor prognosis.
•The ADAURA study marked the advent of precision medicine and molecular biomarker testing to the early stages disease.•The IMPower-010 trial paved the way to the application of immune-checkpoint ...inhibition in the post-operative setting.•The ITACA trial definitively established no role for tailored adjuvant chemotherapy in surgically resected NSCLC.•The Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease.•Growing evidence is supporting MRD as reliable prognostic biomarker in the adjuvant setting.
We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease’s recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.
PDF
