Regional Relapse-free Survival Research Articles

Reduced-Volume Irradiation of Uninvolved Neck in Patients With Nasopharyngeal Cancer: Updated Results From an Open-Label, Noninferiority, Multicenter, Randomized Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/μL v 335 cells/μL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.

The feasibility of level Ib-sparing intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma and high-risk factors classified based on the International Guideline

Background and PurposeTo examine the feasibility of level Ib-sparing intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) who had high-risk factors classified based on the International Guideline (IG). Materials and MethodsWe evaluated 961 non-metastatic NPC cases based on IG recommendations for prophylactic Ib irradiation. Four high-risk factors were used to categorise patients into three cohorts: A, B, and C. Propensity score matching was used to balance baseline characteristics in Cohort C, resulting in a matched Cohort C. Recurrence rates at level Ib and regional relapse-free survival (RRFS) rates were evaluated. ResultsAmong patients with negative Ib lymph nodes (LNs), 18, 54, 420, and 444 exhibited involvement of structures that drain to level Ib as the first echelon (FES), involvement of the submandibular gland (SMG), level II LNs with radiologic extranodal extension (rENE), and level II nodes with a maximal axial diameter (MAD) ≥ 2 cm, respectively. The recurrence rate was highest in Cohort A (11.1 %). Cohort B had no level Ib recurrence. In matched Cohort C, recurrence rates were low in both groups (Ib-sparing group: 0.6 % vs. Ib-covering group: 0.6 %, P > 0.999). No significant differences were observed in 5-year RRFS rates between the two groups in cohort A (p = 0.208), cohort B (p = 0.905), and matched cohort C (p = 0.423). ConclusionsLevel Ib-sparing IMRT could be performed safely for NPC patients with level II LNs who had rENE and/or MAD ≥ 2 cm. Further research should determine the necessity of level Ib prophylactic irradiation for patients with FES or SMG involvement.

The Feasibility of Level Ib Sparing Intensity Modulated Radiation Therapy in Nasopharyngeal Carcinoma Patients with High-Risk Factors: Based on International Guideline

In spite of the rarity of level Ib recurrence after intensity-modulated radiation therapy, the International Guideline (IG) provides the risk factors for prophylactic coverage. In practice, however, there are significant differences between institutions. The purpose of this study is to examine the feasibility of sparing level Ib IMRT in NPC patients with high-risk factors based on IG. From January 2014 to October 2017, newly-diagnostic, non-metastatic NPC patients in our center were retrospectively reviewed. According to the risk factors of prophylactic level Ib coverage in patients with negative level Ib recommended by IG, the characteristics of pre-treatment MRI were analyzed. Four high-risk factors were identified: a. involvement of the structures that drain to level Ib as first echelon (FES), including anterior half of nasal cavity, oral cavity, b. involvement of submandibular gland (SMG), c. with radiologic extranodal extension (rENE) in level II LNs, or d. maximal axial diameter (MAD)≧2 cm in level II LNs. Patients with risk factors were divided into Cohort A (with risk factors a), Cohort B (with risk factor b, but without a), and Cohort C (only with risk factors c and/or d). Recurrence rates of level Ib and regional relapse-free survival (RRFS) rates were evaluated in different cohorts. A total of 961 patients were finally included. Thirty-six cases (3.7%) presented with radiologically positive level Ib metastasis. For the other patients with negative Ib LNs, there were 18, 65, 421, and 444 cases classified as FES involvement, SMG involvement, level II LNs with rENE, and level II nodal with MAD ≧2 cm. Excluding overlap, a total of 571 patients with risk factors were divided into three groups: Cohort A (n = 18), Cohort B (n = 49) and Cohort C (n = 504). Nine patients (9/961, 0.94%) developed level Ib recurrence. Except for 1 patient with positive Ib LNs at diagnosis, 2 did not meet any of the risk factors, while the other six (6/9, 66.7%) met at least one risk factor. The rate of recurrence at neck level Ib was highest in Cohort A (11.1%, 2/18; Ib-sparing group: 0/10, 0.0% vs Ib-covering group: 2/8, 25.0%; P = 0.183). In Cohort B, no cases were found with level Ib recurrence (0.0%, 0/49). In Cohort C, the rates were rare (0.8%, 4/504) in both groups (0.7%, 2/276 vs 0.9%, 2/228; P > 0.999). Among the three Cohorts, there were no significant differences in 5-year RRFS between two groups, which were 90.0% vs 62.5% (p = 0.248), 90.9% vs 92.0% (p = 0.905), and 92.6% vs 90.1% (p = 0.445), respectively. Among patients with high-risk factors, the incidence of grade 3-4 late dry mouth symptom was higher in the level Ib-covering group (3.1% vs 7.5%, P = 0.033). Level Ib sparing appears safe and feasible for NPC patients with negative level Ib LNs, even if combined with risk factors: SMG involvement, and/or level II with rENE, and/or level II MAD ≧2 cm. Level Ib-sparing irradiation reduces dry mouth symptoms compared with level Ib-irradiation.

Feasibility of Omitting Contralateral Neck Irradiation in Patients with Node-Negative Sinonasal Squamous Cell Carcinoma Crossing the Midline

This study aims to analyze the nodal target volume in patients with node-negative SNSCC crossing the midline. One hundred and four patients with node-negative advanced sinonasal squamous cell carcinoma (SNSCC) crossing the midline were included. Survival rates were estimated and compared between treatment groups. Sixty-four patients received contralateral ENI (contralateral ENI group), while forty patients did not (non-contralateral ENI group). The median follow-up time was 89.99 and 95.01 months in the contralateral and non-contralateral ENI groups, respectively. At 5 years, the regional relapse-free survival and contralateral regional relapse-free survival were 57.68% vs. 55.83% (p = 0.372), and 57.68% vs. 61.62% (p = 0.541), in contralateral ENI group vs. non-contralateral ENI group, respectively. Five-year overall survival, local relapse-free survival, and distant metastasis-free survival were similar in the two groups (all p > 0.05). In patients with node-negative SNSCC crossing the midline, omission of contralateral ENI did not affect regional control and survival outcomes on the premise of receiving ipsilateral ENI covering at least levels Ib and II.

Clinical characteristics, prognostic factors, and treatment modalities for head and neck lymphoepithelioma-like carcinoma: A real-world study from southern China

BackgroundWe aimed to elucidate the clinical characteristics, prognostic factors and optimal treatment modalities of head and neck lymphoepithelioma-like carcinoma (HNLELC). MethodsConsecutive patients newly-diagnosed with non-metastatic HNLELC between December 2001 and March 2021 treated with curative intent were retrospectively reviewed. ResultsA total of 288 patients were included, of whom 87 (30.2%) underwent radical surgery alone, 43 (14.9%) underwent definitive radiotherapy with or without concurrent chemotherapy, and 158 (54.9%) underwent surgery followed by postoperative radiotherapy (SRT). Epstein-Barr virus-encoded small RNA (EBER) was positive in 94.8% (239/252) of patients. Cervical node infiltration was seen in 52.8% (152/288) of patients. No significant difference was found in nodal metastasis rate between T1–2 and T3–4 classifications (49.5% vs. 56.5%, p = 0.308). The 3-year overall survival (OS), disease-free survival, locoregional relapse-free survival, and distant metastasis-free survival rates were 89.4%, 78.7%, 89.2%, and 87.7%, respectively. Compared to SRT, surgery alone associated with significant reduced 3-year local (92.8% vs. 96.5%, p = 0.012) and regional relapse-free survival rates (89.3% vs. 96.8%, p = 0.002). Definitive radiotherapy and SRT demonstrated comparable results in all 3-year survival outcomes (all p＞0.05). Multivariate analysis found EBER status was an independent favorable prognostic factor for OS (HR = 0.356, 95% CI: 0.144–0.882, p = 0.026). ConclusionHNLELC was observed to associate with EBV infection and cervical nodal infiltration. Definitive radiotherapy achieved similar survival outcomes compared to SRT, and may serve as a good substitute for patients unfit or unwilling to undergo surgery.

Feasibility of omitting contralateral neck irradiation in patients with node-negative sinonasal squamous cell carcinoma crossing the midline.

Identifying the lymph node target volume in patients with node-negative sinonasal squamous cell carcinoma (SNSCC) crossing the midline poses a challenge. This study aims to address this. We retrospectively reviewed clinically N0 patients with tumors crossing the midline who received elective neck irradiation (ENI) from two centers between 1999 and 2019. The main endpoint was regional relapse-free survival (RRFS). We included 104 patients: 64 received bilateral ENI, and 40 received ipsilateral-only ENI (median follow-up time was 89.99 and 95.01 months, respectively). At 5 years, the RRFS rates were comparable (57.68% vs. 55.83%, p = 0.372), as were the contralateral RRFS (57.68% vs. 61.62%, p = 0.541). Five-year OS, LRFS, and DMFS showed no significant difference between two groups. Our findings provide preliminary evidence suggesting the potential for avoiding contralateral ENI in SNSCC patients with midline crossing tumors who undergo ipsilateral ENI, covering at least level II. Validation through future prospective studies is necessary.

Knowing nodal Rouviére: the power of human intelligence in toxicity reduction.

Patients with nasopharyngeal carcinoma (NPC) represent a distinct group of head and neck cancer patients. They are often non-smokers, non-drinkers, and on average 10 to 20 years younger than those with cancers of other head and neck sites. Given good baseline health status and the effectiveness of contemporary treatment [1], patients with NPC typically have long projected life expectancies and commonly develop late treatment adverse effects, such as dysphagia and swallowing dysfunction. Delineation and coverage of microscopic disease within the clinical target volume (CTV) are crucial in head and neck radiation treatment planning. The retropharyngeal lymph node (RPLN) is the first echelon nodal drainage for NPC. RPLN represents a special entity as they are usually not clinically detectable. Their diagnosis is based on computed tomography (CT) and magnetic resonance imaging (MRI). RPLN was identified almost one hundred years ago. French anatomist Henri Rouviére (1875-1952), through his extensive work in the delineation and classification of human lymph nodes using fresh cadavers, identified a set of lymph nodes in the lateral retropharyngeal space (RPS) [2]. These lateral RPLNs were later named nodes of Rouviére. The nodes of Rouvière, along with the medial RPLN, form the retropharyngeal nodal group, which is located within the RPS. Above the level of the hyoid, RPS contains RPLN and adipose tissues. At the infrahyoid level, the RPS contains only adipose tissues. It is a common practice to delineate the entire RPS up to the level of the hyoid as a CTV target. In this era when technology dominates the field of oncology, tremendous resources have been invested in the development of high-tech radiation delivery machines and pharmaceuticals. Much less effort has been put into the artistry of oncology, such as refining the delineation of target volumes in radiation planning, albeit a significantly less cost-effective and labor-intensive approach [3-6]. Recently, Mao et al. [7], in a multicenter randomized phase III trial, demonstrated how sparing of the medial retropharyngeal nodal group alone in radiation planning – a process that solely relies on human intelligence without any additional human effort or technological resources – results in 39% reduction in ≥ grade one clinician-rated acute dysphagia and 24% reduction in ≥ grade one weight loss. In addition, there was a significant improvement in patient-reported quality-of-life outcomes at 3 years, such as global health status, role-social function and swallowing function. No recurrence was observed in the medial RPLN sparing group. After adjusting for covariates, the regional relapse-free survival rates were similar in medial RPLN sparing and the medial RPLN non-sparing groups [7]. In the study by Mao et al. [7], utilizing the medial RPLN sparing approach, the mean dose to the middle pharyngeal constrictors decreased from 54 Gy to 49 Gy. Why would such a mild decrease in dose result in such modest improvement in clinician- and patient-rated swallowing function? It is a common misunderstanding that swallowing dysfunction from radiation is a direct result of muscle damage. The neural contribution of swallowing dysfunction is commonly overlooked. By sparing pharyngeal constrictor muscles, one also inevitably spares the pharyngeal nerve plexus, which lies on the posterior surface of the middle pharyngeal constrictor muscle. The pharyngeal nerve plexus contains fibers of cranial nerves IX, X, and superior sympathetic ganglion - the main sensory and motor nervous supply of the pharynx. Objective assessment of swallowing function using video fluoroscopic swallow study or high-resolution manometry of pharyngeal swallow pressure would help us to define the objective outcome of this medial RPLN and pharyngeal plexus sparing approach. Developmentally, medial RPLN undergoes atrophy before puberty, and it usually disappears by the age of 5. Lateral RPLN, however, persists in adulthood. Tumor involvement of the medial RPLN is very rare [8]. In a study of 3,100 newly diagnosed NPC, using contemporary MRI techniques, medial PRLN involvement was only identified in 0.2% of the patients, and they were all located at the level of the second or third cervical vertebra [8]. The group by Mao et al. [7], by leveraging and transferring the knowledge of lymphatic development and pattern of tumor spread – human intelligence – into clinical treatment planning and toxicity reduction. Much of the practice in medicine is based on myth and tradition. In the field of radiation oncology, it is common for clinicians to follow the one-size-fits-all rule by following national or protocol guidelines without understanding patterns of tumor spread or employing the-bigger-the-better approach while believing that a larger CTV would result in improved local control. It is not until we combine human intelligence with technological advancements will we see improved tumor control and quality of life in our patients. Annie W. Chan contributed substantially to the conception and drafted the article. The author has nothing to report. The author declares no conflicts of interest. Not applicable. Not applicable. Not applicable. Not applicable.

Upper-Neck Versus Whole-Neck Irradiation at the Contralateral Uninvolved Neck in Patients With Unilateral N3 Nasopharyngeal Carcinoma

Upper-neck irradiation (UNI) at the uninvolved neck has shown similar regional relapse-free survival as standard whole-neck irradiation (WNI) in patients with N0-1 nasopharyngeal carcinoma. However, whether UNI at the contralateral uninvolved neck is feasible in unilateral N3 disease, defined as >6 cm and/or below the caudal border of the cricoid cartilage, remains unclear. Data for 291 patients with nasopharyngeal carcinoma with unilateral N3 disease who were treated with intensity modulated radiation therapy from 2009 to 2015 were retrospectively analyzed. Among them, 190 received bilateral WNI (WNI group); the remaining 101 received WNI at the involved neck and UNI at the contralateral uninvolved neck (UNI group). Survival rates were estimated using the Kaplan-Meier method, and differences between groups were compared using the log rank tests. The median follow-up was 79.4 months (interquartile range, 56.0-89.3). Twenty-five patients had regional lymph node relapses (UNI: 10.9%, 11/101 vs WNI: 7.4%, 14/190; P=.31). Of these, 23 patients relapsed within the previously involved neck regions, while only 2 patients had relapses in the contralateral uninvolved neck (1 each in the UNI and WNI groups). Five-year regional relapse-free survival rates were similar between groups (89.7% vs 92.7%, P=.29). Similar between-group findings were also observed for 5-year overall survival (76.1% vs 80.4%, P=.40), distant metastasis-free survival (74.9% vs 79.2%, P=.44), and local relapse-free survival (95.6% vs 94.7%, P=.64). Furthermore, oncologic outcomes in subgroup and multivariable analyses were similar between groups. Regional control and survival outcomes were comparable in UNI at the contralateral uninvolved neck and standard WNI in patients with nasopharyngeal carcinoma with unilateral N3 disease. Our findings provide evidence for future radiation therapy guidelines of nasopharyngeal carcinoma.

Feasibility of ipsilateral elective neck irradiation of levels Ib and II without level III in patients with node-negative sinonasal squamous cell carcinoma.

The necessity of level III irradiation in patients with node-negative advanced sinonasal squamous cell carcinoma (SNSCC) is unclear. Seventy-eight patients with advanced SNSCC were included. Survival rates were estimated and compared between treatment groups. Twenty-five patients received ipsilateral levels Ib and II irradiation (group 1) and 53 patients received ipsilateral levels Ib and II plus level III irradiation (group 2). The median follow-up time was 75.56 months. Five-year survival rates (regional relapse-free survival, overall survival, local relapse-free survival, and distant metastasis-free survival) were similar between groups 1 and 2 (all p > 0.05). Irradiation doses to the thyroid and larynx were significantly lower in group 1 than in group 2. Ipsilateral irradiation of levels Ib and II neck provides similar regional control and results as irradiation of these levels plus level III, with lower irradiation doses to normal neck tissue, in patients with node-negative advanced SNSCC.

The value of intravoxel incoherent motion model-based diffusion-weighted imaging for predicting long-term outcomes in nasopharyngeal carcinoma.

The aim of this study was to evaluate the prognostic value for survival of parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in patients with nasopharyngeal carcinoma (NPC). Baseline IVIM-DWI was performed on 97 newly diagnosed NPC patients in this prospective study. The relationships between the pretreatment IVIM-DWI parametric values (apparent diffusion coefficient (ADC), D, D*, and f) of the primary tumors and the patients' 3-year survival were analyzed in 97 NPC patients who received chemoradiotherapy. The cutoff values of IVIM parameters for local relapse-free survival (LRFS) were identified by a non-parametric log-rank test. The local-regional relapse-free survival (LRRFS), LRFS, regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were calculated by using the Kaplan-Meier method. A Cox proportional hazards model was used to explore the independent predictors for prognosis. There were 97 participants (mean age, 48.4 ± 10.5 years; 65 men) analyzed. Non-parametric log-rank test results showed that the optimal cutoff values of ADC, D, D*, and f were 0.897 × 10-3 mm2/s, 0.699 × 10-3 mm2/s, 8.71 × 10-3 mm2/s, and 0.198%, respectively. According to the univariable analysis, the higher ADC group demonstrated significantly higher OS rates than the low ADC group (p = 0.036), the higher D group showed significantly higher LRFS and OS rates than the low D group (p = 0.028 and p = 0.017, respectively), and the higher D* group exhibited significantly higher LRFS and OS rates than the lower D* group (p = 0.001 and p = 0.002, respectively). Multivariable analyses indicated that ADC and D were the independent prognostic factors for LRFS (p = 0.041 and p = 0.037, respectively), D was an independent prognostic factor for LRRFS (p = 0.045), D* and f were the independent prognostic factors for OS (p = 0.019 and 0.029, respectively), and f acted was an independent prognostic factor for DMFS (p = 0.020). Baseline IVIM-DWI perfusion parameters ADC and D, together with diffusion parameter D*, could act as useful factors for predicting long-term outcomes and selecting high-risk patients with NPC.

Neck level Ib-sparing versus level Ib-irradiation in intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma with high-risk factors: A propensity score-matched cohort study

AimLevel Ib lymph nodes metastasis is rare in nasopharyngeal carcinoma (NPC). We aimed to evaluate the feasibility of sparing level Ib-irradiation in NPC patients with high-risk factors. Materials and methodsFour hundred forty-three NPC patients with radiologic extranodal extension (rENE) or level II lymph node maximal axial diameter (MAD) ≥ 20 mm treated by intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were included in this study. Propensity score matching (PSM) was applied to balance potential prognostic factors (including age, sex, T and N stage, pretreatment EBV DNA level, and level II rENE and MAD) between patients who received and omitted level Ib irradiation. Kaplan–Meier analysis and the log-rank test were used to compare regional survival outcomes. ResultsPSM resulted in 169 matched pairs of eligible patients. The median follow-up period was 119 months in the matched cohort. The number of level Ib failure in the level Ib-sparing and level-Ib irradiation groups were 3/169 (1.8 %) vs 2/169 (1.2 %), P > 0.999. And the 5-year regional relapse-free survival (RRFS) rates of the two groups were 88.4 % vs 92.6 %, respectively. After PSM, RRFS (hazard ratio [HR]: 1.508, 95 % confidence interval [CI]: 0.762–2.986, P = 0.239), OS (HR: 1.219, 95 % CI: 0.754–1.972, P = 0.418), distant metastasis-free survival (DMFS) (HR: 1.605, 95 % CI: 0.900–2.863, P = 0.109), and local relapse-free (LRFS) (HR: 0.956, 95 % CI: 0.436–2.095, P = 0.910) were similar in the two arms. The incidence of grade ≥ 1 dry mouth after 5 years was higher in the level Ib-irradiation group (27.5 % vs 16.5 %, P = 0.029). However, the incidences of grade 3–4 late toxicities were similar between the two groups. ConclusionNeck level Ib-sparing appears to be safe and feasible in NPC patients with rENE or level II MAD ≥ 20 mm and negative level Ib lymph nodes. Compared with cervical level Ib-irradiation, omission of irradiation to level Ib provides less dry mouth symptom.

Radiation dose escalation for locally advanced nasopharyngeal carcinoma patients with local and/or regional residual lesions after standard chemoradiotherapy: a non-randomized, observational study

BackgroundTo assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment.MethodsFrom November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1–74.25 Gy (median, 70.4 Gy). The boost doses were 4.0–18.0 Gy (median, 9 Gy), 1.8–2.0 Gy/fraction.ResultsFor all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1–2 versus T3–4, N0–1 versus N2–3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002).ConclusionBoost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study.Trial registration: Retrospectively registered.

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment

BackgroundTo cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies.Patients and MethodsFrom 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared.ResultsOne hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT.ConclusionsFor patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

Long-Term Outcome Following Intensity-Modulated Radiotherapy Delivered Using Individualized Clinical Target Volume Delineation Based on Stepwise Spread Pattern of Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal method for clinical target volume delineation in nasopharyngeal carcinoma has not yet been determined. We have developed an individualized CTV delineation protocol based on the stepwise spread patterns of NPC. This study aimed to determine the long-term outcomes and toxicities in NPC patients receiving intensity-modulated radiotherapy with individualized CTV delineation. <h3>Materials/Methods</h3> We retrospectively reviewed the data of patients with newly diagnosed nondisseminated NPC who underwent IMRT using our individualized CTV delineation protocol. A total of 7,262 patients with NPC (79.3% patients in stage III-IVA) treated between April 2009 and December 2015 were included in this study. Dose–volume statistics, clinical outcomes, patterns of failures and toxicities were assessed. To analyze dose distribution of patients with or without local recurrence, propensity score matching (PSM) was performed to compare the dose between the two groups matched by age, sex, histological type, T category, N category, chemotherapy and gross tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (GTVnx) in a 1:1 ratio. <h3>Results</h3> Median follow-up was 67.3 (range, 2.0-118.7) months. The 5-year local relapse–free survival, regional relapse–free survival, distant metastasis–free survival, progression–free survival, and overall survival rates were 93.6%, 94.4%, 86.8%, 77.8%, and 86.0%, respectively. In-field failure is the major locoregional failure pattern, accounting for 92.3% patients of local and 86% of regional recurrence. Age and T classification were independent prognostic for LRFS, DMFS, PFS, and OS in multivariate analysis. Late grade 3 toxicities were mild and included ear injury (1.8%), xerostomia (0.2%), dysphagia (0.2%), brain injury (0.2%), and trismus (0.1%). No grade 4 toxicity occurred during IMRT or follow-up. PSM analysis revealed no significant difference between minimum (P = 0.815), maximum (P = 0.595), and mean (P = 0.700) dose to the planning tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (PTVnx) between patients with local recurrence and the matched patients without local recurrence. <h3>Conclusion</h3> Our stepwise CTV delineation protocol appears to be a promising strategy for improving outcomes in NPC.

Prostate Brachytherapy Boost in the Elderly: Results of a Comparative Study

<h3>Purpose/Objective(s)</h3> To analyze the oncological outcome and toxicity profile in elderly (> 70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost. <h3>Materials/Methods</h3> In this retrospective observational single institution study (Health-data-hub N°F20201008194116), patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with or without androgen deprivation therapy (ADT). The impact of patient age (≤ 70 y vs. > 70 y) was investigated. Oncological outcome focused on biochemical (BRFS), local (LRFS), regional (RRFS) and metastatic relapse-free survival (MRFS) as well as Disease-free (DFS), Cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated. <h3>Results</h3> From 02/09 to 12/21, 519 pts received a HDB boost. Among them, 387 were analyzed (≤70y: 180 pts [47%] vs. >70y: 207 pts [53%]). Regarding NCCN classification, 98 pts (≤70y: 53 pts; >70y: 45 pts; p = NS) and 289 pts (≤70y: 127 pts; >70y: 162 pts; p = NS) were IR and HR pts respectively. Intensity modulated RT was used in 241 pts (62.6%) with pelvic irradiation in 336 pts (86.2%) for a median dose of 45.5 Gy [35 – 57.5] in 23 fractions [15 - 25]. HDB boost was performed under general/spinal anesthesia delivering a single fraction of 14 or 15 Gy for 307 pts (79.3%). ADT was used in 309 pts (≤70y: 133 pts; >70y: 176 pts; p = 0.009) for a median time of 17.1 months [3 - 41] (IR: 6 months; HR: 18.8 months). With a median follow-up (MFU) of 72.3 months [64.6 – 81.1] for the whole cohort, 5-y BRFS, 5-y LRFS, 5-y RRFS and 5-y MRFS were 88% [84 - 92], 97% [95 - 99], 99% [98 - 1], 95% [93 - 98] respectively with 5-y DFS, 5-y CSS and 5-y OS of 84% [80-88], 99% [97-100] and 94% [92 - 97]. With the same MFU of 60 months in both age groups, oncological outcome was not statically different except for the 5-y CSS (≤70y: 97% [94 - 100] vs. >70y: 100%; p=0.05). Late GU toxicity was observed in 124 pts (32.1%) with 9 G3 pts (7.2%). Late GI toxicity was observed in 41 pts (10.2%) with no G3. However, in a subgroup analysis comparing 70y< pts ≤80y vs. >80y pts, a significant difference was noticed in terms of late GU toxicity (29.7% vs. 61.9%; p = 0.006). <h3>Conclusion</h3> For IR and HR prostate cancers, HDB boost leads to high rates of disease control with less than 3% of late G3 GU/GI toxicities. For elderly pts (>70y), HDB boost remains warranted in order to achieve optimal oncological outcome mainly in HR pts, although competing comorbidity factors will significantly impact the OS. However, HDB boost should be carefully discussed in the super senior pts (> 80 y). Due to the increase in life expectancy, the management of prostate cancer in the elderly is a real challenge for patients, clinicians, health care providers and payers. Except for unfit men, elderly patients remain candidates for optimal curative treatment (i.e., regardless of age) after oncogeriatric assessment.

Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute.

The management of nasopharyngeal cancer (NPC) at present is based primarily on radiotherapy, but the technique by which radiation therapy is delivered is different such as intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-CRT). In our study, IMRT and 2D-CRT were compared for their treatment outcome in locally advanced nasopharyngeal carcinoma (NPC) patients. Patients with Stage II to IVA nasopharyngeal cancer (NPC) as per the American Joint Committee on Cancer 7th and 8th edition 2017 treated with IMRT (n = 30) and 2D-CRT (n = 30) between October 2016 and October 2020 were retrospectively analyzed. We matched our patients by using the propensity-score matching method. OS was the primary endpoint of our study. The secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Acute and late radiation toxicities between IMRT and 2D-CRT were also compared. In the propensity-matched cohort of 60 patients, 30 patients received 2D-CRT and 30 patients received IMRT. Compared with the treatment of 2D-CRT, the IMRT group is associated with a better 3-year OS (70% vs. 85% P = 0.045), LRFS (78% vs. 96% P = 0.047), RRFS (78% vs. 95% P = 0.015), DFS (80% vs. 95% P = 0.034), and PFS (84% vs. 90% P = 0.024), while as DMFS (85% vs. 85% P = 0.147) were comparable in both the groups. IMRT was also associated with a lower incidence of late toxicities such as xerostomia and trismus. Our study demonstrates that IMRT yields better long-term overall survival and local control including LRFS, RRFS, DFS, and PFS. In addition, late toxicities induced by irradiation in nasopharyngeal carcinoma (NPC) are lower with IMRT. IMRT may be an effective treatment in nasopharyngeal cancer (NPC) as compared to 2D-CRT, but further studies are needed to establish the association.

Omitting elective neck irradiation in clinically N0 sinonasal adenoid cystic carcinoma: A propensity score-matched analysis

ObjectiveTo explore the effects of elective neck irradiation (ENI) in clinically node-negative (cN0) sinonasal adenoid cystic carcinoma (SNACC). Materials and methodsBetween January 2000 and December 2016, 60 patients with cN0 sinonasal adenoid cystic carcinoma receiving surgery combined with radiotherapy were analyzed retrospectively, there were 39 received ENI (ENI group) and 21 with no ENI (non-ENI group). Propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan-Meier method and Cox proportional hazard model were used to evaluate the impact of ENI on regional relapse risk and survival outcomes. ResultsThe median follow-up time for our cohort was 82.0 months (12.4–190.7 months). Four patients (6.7%) developed neck nodal relapses, with a median time to progression of 38.8 months. Among them, two patients in ENI group but failed out-field. After PSM, 21 patients were matched in each group. The 7-year regional relapse-free survival (RRFS), distant metastasis free survival (DMFS), progression-free survival (PFS), and overall survival (OS) between ENI group and non-ENI group were 85.4% vs 73.3% (p = 0.845), 65.2% vs 65.6% (p = 0.548), 68.3% vs 66.2% (p = 0.425), and 87.3% vs 84.0% (p = 0.953). Multivariate Cox analysis showed ENI was not an independent prognostic factor associated with RRFS, DMFS, PFS and OS. ConclusionOur findings firstly demonstrated the omission of elective neck irradiation in the management of cN0 sinonasal adenoid cystic carcinoma might be safe without compromising disease control and should be further investigated.

Patterns of Local-Regional Relapse Following Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Despite definite radiotherapy, post-treatment recurrence remains a major challenge for patients with nasopharyngeal carcinoma (NPC). This study aimed to evaluate risk factors for local-regional relapse in patients with non-metastatic NPC treated with intensity-modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> We retrospectively analyzed data from 1040 patients with newly diagnosed, non-metastatic, biopsy-proven NPC from 2013 to 2019 (including 7, 133, 475, and 425 cases of stage I, II, III, and IVA disease, respectively, according to the 8th edition of the American Joint Committee on Cancer staging system). All patients received IMRT at a single institution in China (with or without concurrent chemotherapy). Recurrent sites were delineated on imaging and coregistered with the initial treatment planning computed tomography. The recurrences were classified as "in-field failure" if 95% of GTVr (gross tumor volume of recurrence) was within the 95% isodose; "marginal failure" if 20%–95% of GTVr was within the 95% isodose, or "out-field failure" if less than 20% of GTVr was inside the 95% isodose. Univariate and multivariate analyses with the Cox proportional hazards model were performed to identify the independent risk factors. <h3>Results</h3> With a median follow-up of 44 months, 76 patients (7.3%) developed a recurrence. The median interval of relapse was 20.5 months (range: 7–109 months). The 2-year overall survival, local relapse-free survival and regional relapse-free survival were 95.8%, 96.4% and 98.4%, respectively. Local-alone, regional-alone and synchronous local-regional failures accounted for 57.9% (44/76), 32.9% (25/76), and 9.2% (7/76) of recurrent NPC cases, respectively. In these patients, the male:female ratio was 2.4:1 and the median age was 50 years (range: 21–74 years). Among the 62 local-regional failures with available diagnostic images, 53 cases (85.4%) were "in-field", 5 cases (8.1%) had "marginal", 4 cases (6.5%) were as "out-field". Multivariate analysis showed that the non-keratinizing differentiated subtype and the absence of concurrent chemotherapy (CCT) were independent factors for local recurrence after IMRT (differentiated NPC versus undifferentiated NPC HR = 1.987, 95% CI 1.056–3.738, <i>P</i> = 0.033; non-CCT versus CCT HR = 2.098, 95% CI 1.134–3.884, <i>P</i> = 0.018). The rate of lymph nodes associated with liquefaction was 12.4% by the primary tumors but 46.7% at regional recurrence (liquefaction versus non-liquefaction HR = 11.031, 95% CI 4.992–24.372, <i>P</i><0.001). <h3>Conclusion</h3> The major recurrence patterns were in-field failures. The poor local control rates may be associated with the absence of CCT and differentiated carcinoma of NPC. Lymph node with liquefaction was an independent prognostic factor for regional recurrence.

Long-term Therapeutic Outcome and Prognostic Factors of Patients with Nasopharyngeal Carcinoma Receiving Intensity-modulated Radiotherapy: An Analysis of 608 Patients from Low-endemic Regions of China.

To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT). The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively. IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

Radiotherapy as Elective Treatment of the Node-negative Neck in Oral Squamous Cell Cancer.

Previous studies of node-negative oral squamous cell carcinoma have shown a benefit of elective neck dissection compared to observation. Evidence for radiotherapy as single-modality elective treatment of the node-negative neck is so far lacking. In a retrospective material of 420 early-stage oral cancers from 2000 to 2016, overall survival, disease-free survival, and regional relapse-free survival were calculated with the Kaplan-Meier method. At five years, overall survival was 59.7%, disease-specific survival was 77.2%, and regional relapse-free survival was 83.5%. Among those with adjuvant treatment of the neck after surgery of T1-T2 tumours during 2009-2016, regional relapse-free survival at five years was 85.7% for elective radiotherapy of the neck and 87.4% for elective neck dissection. Elective radiotherapy to the neck with a modern technique and adequate dose might be an alternative to neck dissection for patients with early-stage oral squamous cell cancer.