Planned Neck Dissection Research Articles

Usefulness of Upfront Neck Dissection Before Chemoradiation Therapy for Head and Neck Squamous Cell Carcinoma.

Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications. We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement. Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups. The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes.

Effect of radiation therapy on lymph node fluorescence in head and neck squamous cell carcinoma after intravenous injection of indocyanine green: a prospective evaluation

BackgroundIndocyanine green (ICG)-guided surgery has proven effective in the identification of neoplastic tissues. The effect of radiation therapy (RT) on lymph node fluorescence after intravenous injection of ICG has not been addressed yet. The objective of this study was to evaluate the influence of RT on node fluorescence during neck dissection in head and neck squamous cell carcinoma (HNSCC).ResultsTwenty-four patients with planned neck dissection for HNSCC were prospectively enrolled. Eleven were included without previous radiation therapy and 13 after RT. ICG was intravenously administered in the operating room. The resected specimen was analyzed by the pathology department to determine the status of each resected lymph node (invaded or not). The fluorescence of each resected node was measured in arbitrary units (AU) on paraffin blocs. The surface area (mm2) of all metastatic nodes and of the invaded component were measured. The values of these surface areas were correlated to fluorescence values. A total of 707 nodes were harvested, the mean fluorescence of irradiated nodes (n = 253) was 9.2 AU and of non-irradiated nodes (n = 454) was 9.6 AU (p = 0.63). Fifty nodes were invaded, with a mean fluorescence of 22 AU. The mean fluorescence values in the invaded irradiated nodes (n = 20) and the invaded non-irradiated nodes (n = 30) were 19 AU and 28 AU (p = 0.23), respectively. The surface area of metastatic nodes and of the invaded component were correlated to fluorescence values even after previous RT (p = 0.02).ConclusionNo differences were observed between the fluorescence of irradiated and non-irradiated lymph nodes, including invaded nodes. ICG-guided surgery can be performed after failed RT.Trial registrationEudraCT ref. 2013-004498-29, registered 29 November 2013. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004498-29

Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

The standard of care for non-operative management of human papillomavirus-related oropharynx cancer (HPV-OPC) consists of concurrent cisplatin chemotherapy with radiotherapy (RT) to a total dose of 70 Gy. While the oncologic outcomes of this treatment approach have been excellent, there are considerable acute and late toxicities. Here, we report the 5-year survival and toxicity outcomes of 2 prospective HPV-OPC response-adapted de-escalation trials, in which low-risk (LR) patients were treated with dose-reduced RT to 50 Gy, without concurrent chemotherapy. Patients with LR HPV-OPC and ≥50% response to induction by RECIST 1.1 treated per 2 prospective phase II trials as well as on a prospective cohort registry were included for analysis. Patients were considered LR if the following criteria were met: T1-T3, N0-N2b (AJCC 7th edition), and ≤20 pack-year smoking history. Patients were treated with induction chemo- or chemoimmunotherapy followed by RT alone to 50 Gy. In the early trial iteration, patients underwent a planned neck dissection following RT to confirm pathologic clearance of lymph nodes. Clinicodemographic characteristics were summarized using descriptive statistics. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. From January 2015 through March 2020, 73 patients met LR criteria, of which, 54 (74%) had ≥50% response by RECIST and were de-escalated to RT alone. The median follow-up was 58 (range 10-92) months. The median age was 58 (range 38-84) years, and 92.6% were male. 57.4% of patients never smoked, and 42.6% smoked no more than 20 pack-years. The primary site was tonsil for 53.7% and base of tongue for 46.3%. 24.1% were T1, 53.7% were T2, and 22.2% were T3. 1.9% were N0, 5.6% were N1, 11.1% were N2a, and 81.5% were N2b. The 5-year OS, PFS, and LC were 96.3% (95% CI 91.3%-100%), 96.2% (95% CI 91.2%-100%), and 98.1% (95% CI 94.6%-100%), respectively. 2 (3.7%) patients required a G-tube during RT and none at 1 year following completion of RT. Of the 30 patients with a planned neck dissection, 2 (6.7%) had residual pathologic nodal disease. With a median follow-up of 5 years, this analysis demonstrates excellent long-term local control, survival, and swallowing function among patients with low-risk HPV+ oropharynx cancer treated with induction systemic therapy followed by radiotherapy to 50 Gy without concurrent chemotherapy, including a large proportion of patients with N2b disease. Chemo-selection provides a means of identifying a favorable cohort of HPV+ oropharynx cancer patients who can safely receive RT dose de-escalation. Further work is needed to identify this population by other means, including radiographic and genomic factors.

From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment.

55 Outcomes of FDG PET-CT in Surveillance of Residual Nodal Metastases Following Non-Surgical Management of Head and Neck Squamous Cell Carcinoma: A Retrospective Review

Abstract Aim Assessing the role of positron emission tomography-computed tomography (PET-CT) surveillance in detecting residual disease in nodal metastasis, following non-surgical treatment of Head and neck squamous cell carcinoma (HNSCC), such as chemoradiotherapy or radical radiotherapy. To analyse differences in outcomes between HPV positive and HPV negative cancers. Method Retrospective analysis of 327 patients in South Wales, with histologically proven HNSCC was conducted. All patients were treated non-surgically and post-treatment PET-CT scans were obtained. Patients with PET-CT showing incomplete responses had further analysis of outcomes assessed via surgical histology of the nodes. Outcomes in patients with p16 positive disease were recorded to determine outcomes in HPV positive individuals. Results 64 individuals had residual nodal tumours according to PET-CT. 18 out of 43 patients had a negative histology for malignancy, of which 12 showed p16 positive disease. PET-CT showed a false positive in 41.8% of patients, with a positive predictive value of 58%. 225 patients in total were p16 positive, and 38 out of the 64 residual patients had p16 positive disease. There was no significant difference in outcomes between p16 positive and negative patients. Conclusions Our study concurs with similar literature, that primary CRT in N2 and N3 nodal metastasis followed by PET-CT surveillance minimises unnecessary neck dissections and triple modality treatment. Further research needs to be conducted however, to determine the efficacy of PET-CT surveillance compared to planned neck dissections. Furthermore, outcomes in p16 positive patients requires additional ongoing research to best determine surveillance techniques and long-term health outcomes.

Does Bulky Adenopathy in Human Papilloma Virus-Positive Oropharyngeal Squamous Cell Carcinoma Require a Planned Post-Treatment Neck Dissection for Occult Residual Disease?

A planned neck dissection was traditionally considered for a large nodal disease after definitive chemoradiation, yet controversy exists for the human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV OPSCC). We aimed to measure the frequency of persistent occult neck disease in planned neck dissection for HPV OPSCC presenting with a large (≥3.0cm) nodal burden. We designed a retrospective cohort study at a single tertiary referral institution. The study population was sampled from 2006 to 2018 and subjects with HPV OPSCC and adenopathy ≥3.0cm. Inclusion criteria encompassed subjects who completed primary chemoradiation therapy (CRT) or primary radiation therapy (RT), and subsequently underwent a planned neck dissection. We excluded subjects who did not complete therapy or had less than 1-year follow-up. Our primary predictor variable was the size of cervical adenopathy on presentation (3.0-3.9cm, 4.0-4.9cm, 5.0-5.9cm, and ≥6.0cm). Our primary outcome of interest was the presence of disease based on the histopathology review. Other variables included the demographics, primary treatment with CRT or RT, and post-treatment clinical or radiographic evidence of disease. Chi-square testing was used to compare rates of persistent disease, with varying sizes of cervical adenopathy on presentation. The alpha level for statistical significance was set at 0.05. A total of 86 subjects were analyzed, with forty-one females and forty-five males, ranging from 36 to 77years (mean 54.6years). From the total study sample, 35% showed persistent disease, and 67% of those subjects had occult disease at the time of planned neck dissection. Greater than 20% of subjects had persistent disease when the nodal burden was ≥3.0cm at presentation. Furthermore, there was a statistically significant difference in the rates of persistent microscopic disease among subjects with nodal burden of different sizes based on chi-square testing (P=.01, χ2=10.66). Our data suggest that subjects with HPV OPSCC presenting with a nodal burden ≥3.0cm are likely to have 23% chance of persistent occult neck disease after primary CRT or RT. These findings may support the routine treatment of these subjects with a planned neck dissection after initial therapy to confirm or surgically complete disease eradication.

Intra-Treatment Tumor Apparent Diffusion Coefficient, a Quantitative Imaging Metric, is Associated with Neck Nodal Recurrence in De-Escalated Treatment of HPV-Positive Oropharyngeal Cancer (OPC)

<h3>Purpose/Objective(s)</h3> De-escalation strategies for the treatment of HPV-associated OPC show promise for effective, less toxic treatment. However, identifying accurate markers of more aggressive subsets of HPV OPC remains challenging. The 30 Reduction in Radiation for OPC (ROC) trial prospectively used intra-treatment ¹⁸F-FMISO imaging to selectively de-escalate patients to 30Gy chemoradiotherapy, however, a subset of patients still developed nodal recurrence. We hypothesized that diffusion-weighted (DW) MRI-derived quantitative imaging metrics, such as apparent diffusion coefficient (ADC), a surrogate marker of tumor cellularity based on water diffusion patterns, might help identify patients at high risk of recurrence and enable broader use of de-escalation strategies<b>.</b> <h3>Materials/Methods</h3> The 30 ROC trial enrolled patients with p16-positive OPC, cT0-2, N1-2c (AJCC 7^th ed). All patients had pre-treatment ¹⁸F-FMISO (fluoromisonidazole) PET scan and those with baseline nodal hypoxia underwent a 2^nd intra-treatment scan. All patients underwent primary site surgery where negative margin was not required. All patients had gross neck nodal disease. Those with intra-treatment resolution of nodal hypoxia or without initial hypoxia were de-escalated to 30Gy (non-hypoxic group) with 2 cycles of concurrent chemotherapy, while those with persistent radiographic hypoxia (hypoxic group) were treated to 70Gy. Standard T1, T2 weighted, and multiple b-value DW-MRI data were acquired pre-treatment and weekly during the first 4 weeks of treatment. Two radiation oncologists delineated nodal tumor regions of interest (ROIs) in a blinded fashion with ITK-SNAP on DW images (b= 0 s/mm²). Multiple b-value DW data were fitted to a monoexponential model to calculate ADC (mm²/s). The data analysis was performed on ROIs and voxel-wise using the in-house developed tool MRI-QAMPER. Standard statistical analysis was performed using MRI and clinical response data based on RECISTv1.1 provided by a radiologist. <h3>Results</h3> 158 patients were enrolled, of whom 95 had pre-treatment DW-MRI data available with tumor ROI with ADC values. Based on overall ¹⁸F-FMISO imaging, 12.6% (12/95) exhibited persistent hypoxia and 87.4% (83/95) had resolved/no hypoxia. All patients with nodal recurrences were in the de-escalated non-hypoxic group (8/83). Pre-treatment ADC was not different between overall hypoxic and non-hypoxic groups. Among de-escalated patients, those who developed nodal recurrence exhibited significantly different intra-treatment ADC at week 3 (before completing 30Gy) relative to those who did not recur (P<0.05, Wilcoxon rank-sum test). <h3>Conclusion</h3> The quantitative imaging metric, ADC, reflects both the restricted and hindered Brownian motion of water molecules in tumor tissue. Thus, ADC may be a useful intra-treatment marker to identify patients at risk for nodal recurrence to benefit from the incorporation of an upfront planned neck dissection after 30Gy as part of the de-escalation strategy.

Clinical application of circulating tumour DNA in assessment of therapeutic response in HPV positive oropharyngeal cancer

Background: Contemporary management of oropharyngeal squamous cell carcinoma (OPSCC) involves radiation or chemoradiation for the majority of patients, followed by assessment of treatment response at 12 weeks following completion of treatment. Although this has proved to be an oncologically safe approach in comparison with planned neck dissection, a significant number of patients are considered to have an indeterminate response on initial post-treatment assessment. This is a particular problem in the increasingly common HPV related OPSCC.

Hypofractionated chemoradiation for head and cancer: Data from the PET NECK trial.

There has been increased interest in hypofractionated accelerated chemoradiation for head and neck cancer during the recent first peak of the COVID-19 pandemic. Prospective data regarding this approach from randomised trials is lacking. In the PET NECK study, 564 patients with squamous cell carcinoma of the head and neck receiving definitive chemoradiation were randomised to either planned neck dissection or PET CT scan guided surveillance. In this surgical trial, three radiotherapy fractionation schedules delivered over 7, 6 or 4 weeks were permitted with synchronous chemotherapy. The purpose of this study was to determine efficacy and quality of life outcomes associated with the use of these schedules.Primary local control and overall survival in addition to quality of life measures at immediately post treatment and 6, 12 and 24 months post-treatment were compared between the three fractionation cohorts.In the 525 patients where fractionation data was available, 181 (34%), 288 (55%) and 56 (11%) patients received 68–70 Gy in 34–35 fractions (#), 60–66 Gy in 30# and 55 Gy in 20# respectively. At a minimum follow up of two years following treatment there was no significant difference between the three fractionation schemes in local control, overall survival or any quality of life measure.Despite the obvious limitations of this study, some data is provided to support the use of hypofractionated accelerated chemoradiation to avoid delays in cancer treatment and reduce hospital visits during the peak of a pandemic. Data from on-going randomised trials examining hypofractionated chemoradiation may be useful for selecting fractionation schedules during future pandemics.

Evaluation of incidence of metastatic involvement of level IIb subgroup lymph nodes in squamous cell carcinoma of the oral cavity

Background: To determine the overall incidence of level IIb lymph node metastases in N0/N+ neck and whether level IIb node removal is necessary in oral squamous cell carcinoma (OSCC) patinets. Material and methods: A prospective analysis of 182 biopsy proven OSCC patients who underwent surgical excision of the primary lesion with safe margins. Based on the site, nodal involvement etc the planned neck dissection has been performed. Resected primary lesion and different levels of removed lymph nodes was marked and sent for histopathological examination. 26 (14.3%) patients underwent bilateral neck dissection and unilateral in remaining 156 patients (85.7%). Results: 22 patients in our study specifically had metastases in level IIb, representing 22 out of 182 patients (12%) and 22 out of 208 neck dissection specimens (10.5%), combining pathologically N0 necks and clinically node-positive necks. 31 patients reported with a local recurrence at 1-year follow-up period, whereas remaining 151 patients had no loco regional residual disease at 1 year follow up. All the patients with recurrent disease were provided palliative treatment. Conclusions: Our results indicate the importance of always dissecting level IIb nodes in case of high metastatic rate of patients with clinically positive neck nodes, exclusively staged as N2b or greater. However, for a therapeutic neck dissection, level IIb clearance should always be done if there are positive lymph nodes at level IIa clinically or intra-operatively on frozen section.

Mature results of the LCCC1413 phase II trial of de-intensified chemoradiotherapy for HPV-associated oropharyngeal squamous cell carcinoma.

6022 Background: To report the mature results from a prospective phase II clinical trial of highly de-intensified chemoradiotherapy (CRT) for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: The major inclusion criteria were: 1) T0-T3, N0-N2, M0, 2) p16 positive, and 3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatin 30 mg/m2(second choice was cetuximab). Patients with T0-T2 N0-1 disease did not receive chemotherapy. All patients had a 10 to 12-week post-treatment PET/CT to determine need for planned neck dissection. The primary study endpoint was 2 year progression free survival (PFS). Secondary endpoint measures include 2 year local control (LC), regional control (RC), distant metastasis free survival (DMFS), cause specific survival (CSS) and overall survival (OS), and patient reported symptoms (PRO-CTCAE) and quality of life (EORTC QLQ-C30 &amp; H&amp;N35). Results: 114 patients were enrolled (median f/u of 28.8 months, range 2.6 to 51.4) with 84 having a minimum follow-up of 2 years. Smoking status was as follows: 47% never, 33% ≤ 10 pack years, and 19% &gt; 10 pack years. Post-treatment PET/CT complete response rate was 93% at the primary site and 80% in the neck. Eleven patients had planned neck dissection with 4 having pathological residual disease. Two year LC, RC, DMFS, PFS, CSS, and OS were the following: 96%, 99%, 91%, 88%, 97%, and 95%. Neither smoking status nor receipt of cetuximab correlated with recurrence. Four patients with recurrent disease had PIK3CA mutations. Thirty four percent of patients required a feeding tube (none permanent) for a median of 10.5 weeks. Mean pre- and 2-year post-treatment EORTC QOL scores were: Global 79/83 (lower worse), Swallowing 8/9 (higher worse), Dry Mouth 14/45 (higher worse), and Sticky Saliva 9/28 (higher worse). Mean pre- and 2 year post-treatment PRO-CTCAE (0 to 4 scale, higher worse) scores were: Swallowing 0.5/0.7 and Dry mouth 0.4/1.4. There were no ≥ Grade 3 late adverse events. Conclusions: Clinical outcomes with a highly de-intensified CRT regimen of 60 Gy IMRT with concurrent low-dose cisplatin are excellent in patients with HPV-associated OPSCC. Clinical trial information: NCT02281955.

Diagnosis of cervical lymph node metastases in head and neck cancer with ultrasonic measurement of lymph node volume

ObjectiveThe purpose of this study was to evaluate the usefulness of ultrasound (US) volume measurement of the cervical lymph nodes for diagnosing nodal metastasis in patients with head and neck cancer using a node-by-node comparison. MethodsThirty-four consecutive patients with head and neck cancer from one tertiary university hospital were prospectively enrolled from 2012 to 2017. Patients with histologically proven squamous cell primary tumors in the head and neck region scheduled to undergo a therapeutic neck dissection were eligible. For each patient, 1–4 target lymph nodes were selected from the planned neck dissection levels. Lymph nodes with thickness >20 mm or in a cluster were excluded. Node-by-node comparisons between the pre-operative US assessment, the post-operative actual measurements and histopathological results were performed for all target lymph nodes. Quantitative measurements, such as three diameters, ratios of the three diameters and volume were analyzed in this study. Lymph node volume was calculated using the ellipsoid formula. ResultsPatients comprised 28 men and 6 women with a mean age of 60.0 years (range, 29–80 years) at the time of surgery. In total, 67 target lymph nodes were analyzed in this study and the thickness ranged from 3.9 to 20.0 mm (mean 8.0 mm). There was a strong correlation between the US volume and post-operative actual volume (ρ = 0.87, p < 0.01). The US volume measured 2156 ± 2156 mm3 for the tumor positive nodes, which was significantly greater than the US volume of 512 ± 315 mm3 for tumor negative nodes (p < 0.01). Significant differences between tumor positive and tumor negative nodes were found in five variables (volume, thickness, major axis, minor axis and ratio of minor axis to thickness) for total lymph nodes. To identify predictors of lymph node metastasis, ROC curves of the US variables of target lymph nodes were compared, of which 4 variables were considered acceptable for predicting the lymph node metastasis: volume (AUC 0.86), thickness (AUC 0.86), major axis (AUC 0.79), and minor axis (AUC 0.79) for total lymph nodes. The optimal cut-off level for US volume in total lymph nodes was found to be 1242 mm3, whereby a 62% sensitivity and 98% specificity was reached (likelihood ratio: 25.2). ConclusionPre-operative ultrasonic volume measurement of the cervical lymph nodes was useful for early detection of cervical nodal metastasis in head and neck cancer.

Wound fluid enhances cancer cell proliferation via activation of STAT3 signal pathway in vitro.

Wound healing begins immediately after surgery with a modification of the microenvironment via a well‑orchestrated interaction between cells, cytokines and growth factors. Some of these growth factors and cytokines have mitogenic effects on cancer cells, which may lead to enhanced cancer cell proliferation and early metastatic events. The present study aimed to investigate the effects of wound fluid (WF) on the head and neck squamous carcinoma cell lines FaDu and HLaC78 in vitro. WF was harvested from 7 patients who had undergone a planned neck dissection. The presence of cytokines and growth factors was evaluated with the dot blot assay. Proliferation and cell viability were investigated via MTT assay and Ki-67 staining. Cell invasion was measured via tree‑dimensional invasion assay. Western blotting was used to investigate STAT 3 activation. WF contained several cytokines and growth factors responsible for pro‑ and anti‑inflammation, chemotaxis, proliferation and angiogenesis. The proliferation effect of WF on FaDu and HLaC78 was concentration dependent. Media with 40% WF resulted in the highest proliferation effect. FaDu and HLaC78 exhibited enhanced motility after cultivation with 40% WF compared with cultivation with expansion medium. Cultivating cancer cells with WF had no advantageous effect on cell viability after the paclitaxel treatment. Western blot analysis revealed enhanced activation of the STAT3 signaling pathway by WF in both FaDu and HLaC78. In conclusion, surgery leads to excessive release of mitogenic factors. The contact of non‑resected cancer cells and these factors may have a negative impact on patient outcome. Future investigations should specifically focus on the inhibition of mitogenic factors following cancer surgery in order to prevent early metastasis and cancer recurrence.

Pretreatment FDG PET-Based Metabolic Nodal Sub-Tumor Volumes Improve Node-Specific Failure-Free Survival Prediction in Low-Risk Oropharyngeal Cancer Patients Following Chemoradiation Therapy

To compare the performance of lymph-node specific and conventional total node FDG-PET metabolic tumor volume (MTV) for failure-free survival (FFS) prediction in low-risk oropharyngeal cancer patients. Pretreatment FDG-PET scans of 144 HPV-associated oropharyngeal cancer patients with ≤10 pack-year smoking history and treated with definitive chemoradiation therapy (chemo-RT) to 70 Gy IMRT were retrospectively analyzed. Patients with upfront surgical excision of the primary tumor or planned neck dissection were excluded. The primary tumor and each PET-avid lymph node (totaling 481) were contoured and labeled by a radiation oncologist. Conventional nodal MTV (MTVC) was calculated using a combined lymph node 50% maximum standardized uptake value (SUV50%) threshold. Lymph-node-specific MTV (MTVI) was calculated using SUV50% from each lymph node. Finally, modified nodal MTV (MTVM) was calculated as the sum of all MTVI for each patient. Recurrence patterns including nodal failure location and time to biopsy-proven failure were analyzed. Nodal failure was defined as positive pathology in an unplanned neck dissection. ROC analysis was performed to assess the predictive performance of MTVC and MTVM for patient-level nodal failure within one year as a binary endpoint right censored by follow-up time, distant metastasis, new primary tumor, or death within one year. ROC analysis was also used on MTVI for node-specific failure prediction. Using Kaplan-Meier analysis, Mantel-Haenszel hazard ratios (HRs) were calculated for three evenly distributed quartile cut points to compare relative risks for patient-level and node-specific FFS. Statistical significance was assessed at a confidence level of 95% using Bonferroni correction for multiplicity. Confidence intervals of the ROC area under the curve (AUC) were calculated using bootstrap resampling. Eleven nodal failures (7.6% of patients, 3.3% of lymph nodes) occurred within a median (interquartile) of 5.0 (4.0-11.2) months from chemo-RT initiation. For one-year patient-level failure, modified MTV did not improve prediction performance (MTVC-AUC = 0.758 (95% CI: 0.636-0.882), MTVM-AUC = 0.682 (95% CI: 0.517-0.847)). MTVC>11.2 cc was associated with statistically significant HR of 7.6 (95% CI: 1.76-32.8), p<0.019; however, MTVM was not statistically significant for any of the tested cut points. For node-specific failure, MTVI-AUC= 0.833 (95% CI: 0.697-0.968), and MTVI > 6.6 cc was associated with HR of 14.43 (95% CI: 3.62-57.6), p<0.001. Modified MTV using additive node-specific thresholding did not improve patient-level nodal FFS prediction, indicating that conventional nodal MTV may be adequate. However, node-specific MTV was strongly predictive of node-specific failures, which may guide differential dosing regimens for oropharyngeal RT in low-risk patients. As such, radiation dose de-intensification may not be indicated for some highly metabolic tumor sub-volumes.

Prognostic role of extracapsular spread in planned neck dissection after chemoradiotherapy.

The purpose of this study is to evaluate the prognostic significance of nodes with extracapsular spread (ECS) in patients treated with a planned neck dissection after chemoradiotherapy. We carried out a retrospective study of 109 cN+ patients who achieved a complete response in the primary location after chemoradiotherapy and treated with a planned neck dissection. The 5-year disease-specific survival for patients without residual metastatic nodes in the neck dissection (pN0, n = 69) was 75.7% (95% CI: 64.4%-87.0%). For patients with metastatic nodes without ECS (pN+/ECS-negative, n = 17), the corresponding figure was 74.0% (95% CI: 48.2%-99.8%), and for patients with metastatic neck nodes with ECS (pN+/ECS-positive, n = 23) it was 8.7% (95% CI: 0.0%-24.3%) (P = .0001). The presence of ECS in the pathologic study of the planned neck dissections carried out after chemoradiotherapy in patients with human papillomavirus-negative (HPV-negative) head and neck squamous cell carcinoma (SCC) allows identification of a group of patients with a high risk of failure.

Initial Results from a Phase 2 Prospective Trial of De-intensified Chemoradiation therapy for Low-Risk HPV-associated Oropharyngeal Squamous Cell Carcinoma

To report initial results from a prospective phase 2 clinical trial of highly de-intensified chemoradiation therapy (CRT) for patients with favorable risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). The major inclusion criteria were: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatin 30 mg/m2 (second choice was cetuximab). Patients received neither induction chemotherapy nor definitive surgery. Patients with T0-T2 N0-1 disease did not receive chemotherapy (i.e. received 60 Gy alone). All patients had a 10- to 12-week posttreatment PET/CT to determine need for planned neck dissection. The primary study endpoint is 2-year progression-free survival (PFS). Secondary endpoint measures include 2-year local control (LC), regional control (RC), distant metastasis free survival (DMFS), and overall survival (OS), and patient reported symptoms (PRO-CTCAE) and quality of life (EORTC QLQ-C30 & H&N35). Data analysis was performed for patients with a minimum of 1 year of follow-up. One hundred and thirteen patients have enrolled, with 82 having a minimum follow-up of 1 year. Smoking status was as follows: 49% never, 35% ≤ 10 pack-years, and 16% > 10 pack-years. Forty-four percent were HPV and p16 positive and 56% were HPV negative/unknown and p16 positive. Posttreatment PET/CT complete response rate was 97% at the primary site and 81% in the neck. Eight patients had planned neck dissection with 1 having pathological residual disease. Twoyear PFS, LC, RC, DMFS, CSS, and OS are the following: 93%, 98%, 99%, 95%, 96%, and 95%. Sixteen patients were treated with RT alone and all remain in cancer control. Mean pre- and 1-year posttreatment EORTC QOL scores were: Global 79/82 (lower worse), Swallowing 8/12 (higher worse), Dry Mouth 15/55 (higher worse), and Sticky Saliva 10/33 (higher worse). Of all patients, 39% patients required a feeding tube (none permanent) for a median of 10.5 weeks (range 3-42 weeks). Mean pre- and 1-year posttreatment PRO-CTCAE (0 to 4 scale, higher worse) scores were: Swallowing 0.5/0.9 and Dry mouth 0.5/1.6. There were no ≥ Grade 3 late adverse events. Initial clinical outcomes with highly de-intensified CRT are excellent in favorable risk OPSCC with evidence of better preservation of quality of life compared to standard therapies (ClinicalTrials.gov, NCT02281955).

Accuracy of FDG PET-CT response assessment following radiotherapy alone for head and neck squamous cell carcinoma: Retrospective analysis of 45 patients.

FDG PET-CT is an established tool for response assessment following definitive concurrent chemoradiotherapy for head and neck squamous cell carcinoma with a high negative predictive value guiding treatment decisions. Little data is available regarding the accuracy of FDG PET-CT for response assessment following definitive radiotherapy without chemotherapy. We retrospectively analysed the accuracy of FDG PET-CT for response assessment following radiotherapy alone without planned neck dissection in 45 patients. PET-CT had a high negative predictive value of 93% and positive predictive value of 88%. Based upon the high negative predictive value, PET-CT can be used to avoid surgical intervention following radiotherapy alone.

Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender(P=0.215), age(P=0.828), primary tumor site(P=0.927), LR(P=0.126), DFS(P=0.710), and OS(P=0.402) between the two groups, while the RR(χ(2)=5.640, P<0.05) and distant metastasis(χ(2)=10.363, P<0.01) showed significant differences between the two groups. Conclusion: The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.

Outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease

BackgroundThe present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease.MethodsA retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression.ResultsWe identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8–135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemoradiotherapy (p = 0.10). Primary, regional, and distant control at 5 years was 71%, 66%, and 53%, respectively. There was a trend towards improved regional control with primary surgery (p = 0.07). Planned neck dissection following primary chemoradiotherapy did not improve regional control (p = 0.55). Patients with p16-positive tumors exhibited improved overall (p = 0.05) and metastatic recurrence-free survival (p < 0.05). There were no factors predictive of treatment assignment nor factors associated with overall survival, local and regional control, or distant metastases free-survival on univariate analysis.ConclusionsPatients with N3 head and neck squamous cell carcinoma exhibit 5-year overall survival rates of approximately 30% regardless of treatment modality. Planned neck dissection does not improve regional control in patients undergoing definitive chemoradiotherapy. p16-positive patients represent a favorable cohort. Distant failure comprises the major failure pattern and should be the focus of future studies in improving the outcome of this patient cohort.