Lower Neck Nodes Research Articles

COVID-19 vaccination and low cervical lymphadenopathy in the two week neck lump clinic - a follow up audit

The UK COVID vaccination programme has progressed at an astonishing rate since the first patients received their doses in December 2020. It is well known that other vaccines including influenza and human papilloma virus (HPV) can result in reactive lymphadenopathy in the axilla and/or neck. Patients are now presenting via the two week wait neck lump clinic with supraclavicular fossa and low neck lymphadenopathy related to COVID vaccination, and to similar one stop breast clinics with axillary lymph nodes. In an audit of 80 patients seen over a period of one month, we found COVID vaccine-related low neck lymphadenopathy in four cases (5%), with an additional rectal cancer patient thought to have metastatic disease who presented with a Virchow type node. COVID vaccine-related lymphadenopathy should be considered in the differential diagnosis of low-neck nodes if they occurred shortly after vaccination, but it is important to exclude sinister disease using ultrasound and other investigations as necessary.

Clinical Outcomes of Conventional Low Anterior Neck Field and Intensity Modulated Radiation Therapy in Oropharyngeal Cancer Patients

Radiotherapy (RT) to the uninvolved low neck can be delivered either by whole-neck intensity-modulated radiotherapy (WN-IMRT), or by matching a photon low anterior neck (LAN) field to the IMRT field. Potential benefits of the latter approach are the ability to deliver lower radiation dose to midline structures and improved dose distribution in the superior neck. However, the uncertainty of dose delivery at the match line and inadequate cover to the posterior low neck with this technique, has raised concern regarding the possibility of neck recurrences. Dosimetric studies comparing WN-IMRT with IMRT+LAN field have been published but clinical data on safety of the LAN field technique is lacking. The purpose of this study is to report outcomes following elective radiation to the lower neck using IMRT+LAN field in patients with squamous cell carcinoma (SCC) of the oropharynx (OP) and to evaluate recurrence risk at or below the match line with this technique. This is a single-centre retrospective study of OP SCC patients treated with bilateral neck IMRT between April 2005 and November 2014. p16 immunohistochemistry was performed prospectively after 2010. Our policy suggests using a LAN field in all cases with uninvolved low neck nodes (low level 3 and levels 4a/b, 5a-c) with the matching line placed at least 2cm below the inferior end of GTV. The LAN field delivers 45.5Gy in 21 fractions over 4.5 weeks). The half-beam IMRT fields encompass the high risk CTV (macroscopic disease with an isotropic margin of 10mm and involved nodal levels) treated to 65Gy in 30 fractions over 6 weeks, and the low-risk CTV (upper neck uninvolved nodes) treated to 54Gy in 30 fractions over 6 weeks. Out of 221 OP cancer patients treated with curative RT, 148 (67%) were treated with IMRT+LAN field. Median follow up was 41 months. Median age was 58 years (range, 26-86). 36 (24%) had T1, 59 (40%) T2, 21 (14%) T3 and 32 (22%) T4 disease. 20 (14%) had N0, 19 (13%) N1, 16 (11%) N2a, 73 (49%) N2b and 20 (14%) N2c disease. Of the 81 patients for whom p16 immunohistochemistry was available, 64 (79%) were p16 positive and 17 (21%) p16 negative. 109 (74%) of patients received induction chemotherapy with cisplatin and 5-fluorouracil, 128 (87%) received concomitant chemotherapy (cisplatin 29, carboplatin 98, cetuximab 1). After a median follow up of 41 months, the 3-year recurrence-free survival (RFS), regional recurrence-free survival (RRFS) and overall survival (OS) were 81.4%, 92.6% and 88.9%. The 5-year RFS, RRFS and OS were 77.6%, 86.2% and 91.2% respectively. No recurrences were seen in the LAN field and no recurrences were seen in the match line between the IMRT fields and the matched LAN field. RT to uninvolved lower neck nodal levels in selected OP SCC patients using a LAN field leads to excellent outcomes with no recurrences seen at the field match line or the low neck.

T-category Remains an Important Prognostic Factor for Oropharyngeal Carcinoma in the Era of Human Papillomavirus

AimsTo determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. Materials and methodsOSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. ResultsIn total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05–0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14–0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22–1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08–2.99), death (hazard ratio 1.37, 95% confidence interval 1.06–1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00–1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. ConclusionTumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status.

Should the Contralateral Lower Neck Nodes Be Irradiated in Postoperative Radiation Therapy for Tongue Cancer?

Should the Contralateral Lower Neck Nodes Be Irradiated in Postoperative Radiation Therapy for Tongue Cancer?

The Reproducibility of Patient Setup for Head and Neck Cancers Treated with Image-Guided and Intensity-Modulated Radiation Therapies Using Thermoplastic Immobilization Device

The reproducibility of patient setup is an important issue for head and neck cancers treated with intensity-modulated radiation therapy (IMRT). In this study, an image-guided radiation therapy (IGRT) system has been used to minimize the uncertainty of patient setup while standard thermoplastic masks were used to provide adequate immobilization for the head and neck. However, they do not provide sufficient immobilization of the shoulders, which is an important requirement in comprehensive nodal irradiation. Therefore, we investigated the setup and rotational shifts in head and neck cancer patients undergoing IMRT for which this immobilization device had been used together with an IGRT system. The setup and rotational shifts of patients were analyzed using the ExacTrac X-ray 6D IGRT system. The patients were classified as having head and neck tumors in the upper or lower regions. The upper neck nodes included lymph nodal level II while the lower neck nodes included lymph nodal levels III and IV. Clinical data from 227 treatment sessions of 12 head and neck cancer patients were analyzed. The random translational error in inter-and intra-fraction errors of the anterio-posterior (AP) direction might influence the rotational errors of pitch and roll in the upper region. At the same time, the random translational error in the inter-and intra-fraction errors of the AP direction might influence the rotational error of roll in the lower region. We believe that these random translational errors should be considered during treatment. We found variability in random translational errors for different regions in the anatomy of head and neck cancer patients due to rotational shifts. Depending on the location of the primary lesion or the selected nodal treatment targets, these relative positional variations should be considered when setup and rotational shifts are corrected with IGRT systems before treatment.

Nasopharyngeal cancer: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Nasopharyngeal cancer: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Head and neck cancer with lower neck nodal metastases: Management of 23 cases and review of the literature

To investigate the patient outcomes associated with the applied modes of therapy in head and neck cancer with lower neck nodal metastases. The medical records of 23 consecutive individuals who were managed by intent to treat for head and neck cancer with metastatic disease in the lower neck nodes over a 19-year period were reviewed. The mean age was 53.5 years, and the larynx was the most frequently affected primary site (57%). Overall, locoregional tumor control was achieved in the majority (75%) of the cases and the 2-year survival rate was 48%. The 2-year survival rates of people managed by surgery and postoperative radiotherapy, chemoradiation or single modality therapy were 63%, 56% and 17%, respectively, (p=0.04). Aggressive therapy resulted in five (22%) long-term (>5 years) survivors. The combination of treatment modalities proved to be effective management for head and neck cancer with lower neck nodal metastases and should be further investigated in prospective trials.

Bilateral neck metastases in upper aero‐digestive tract cancer: Emphasis on the distribution of lymphatic metastases and prognostic implications

Bilateral neck metastases (BNM) in patients with upper aero-digestive tract cancer (UADTC) indicate a poor prognosis. However, the prognostic significance of involved neck node levels has not been determined clearly. In this study, the distribution of neck nodal metastasis and its impact on prognosis were investigated. Eighty-two previously untreated UADTC patients with BNM from 2000 to 2007 were included in these analyses. The pathology was mainly squamous cell carcinomas, including nasopharynx undifferentiated carcinoma and excluding salivary and thyroid carcinomas. The distribution and pattern of neck metastases and their prognostic significance were assessed, along with other clinical variables. BNM confined to the upper neck level (I-III) showed a lower rate of distant metastasis compared to BNM beyond I-III levels (13.6% vs. 47.4%, P = 0.001). There was a significant reduction in survival among patients with bilateral lower neck (IV-V) metastases on multivariate analysis (HR: 5.95, 95%CI: 1.51-23.43). However, multi-level involvement itself did not correlate with survival. Subgroup analysis (according to nasopharynx and non-nasopharynx cancer) also confirmed the strong trends of lower neck nodal involvement for poorer survival in both groups. BNM at lower neck nodes can be a significant prognostic factor for early systemic dissemination and worse prognosis in UADTC patients.

Utility of PET in unknown primary with cervical metastasis: A retrospective study

FDG-PET is recommended as an investigation in unknown primary tumors, but its definitive role and cost effectiveness are yet to be established. dditional value of FDG-PET over conventional imaging in unknown primary tumors with cervical metastasis. Retrospective study in a tertiary level oncology centre. A total of 112 patients were divided into three groups; 53 with conventional modalities (either computed tomography or magnetic resonance imaging) (group I), 59 with FDG-PET (group II), and group III (subgroup of group II) with both (40 patients). Sensitivity and specificity of both conventional modality and PET were calculated. Association between neck nodes and distant metastasis was analysed using multivariate logistic regression analysis. Sensitivity and specificity for conventional modalities was 92.3% and 50% and sensitivity and specificity of FDG-PET was 92.8% and 71.4%, respectively. FDG-PET detected metastasis in 52.54% of patients. Multivariate logistic regression analysis showed statistically significant association between distant metastasis and multiplicity of nodes (N2b, N2c) (P = 0.007). Among all patients with low neck nodes in group II, FDG-PET detected primaries in 12 patients, 9 of which were infraclavicular (75%). FDG-PET added information to conventional imaging in 32.5% of patients and influenced an overall change in management in 38.9% of patients. FDG-PET is a valuable tool influencing change of management in unknown primary with cervical metastasis. It is recommended especially in the presence of low or multiple neck nodes in view of high incidence of infraclavicular primary and distant metastasis, respectively.

Matching IMRT fields with static photon field in the treatment of head-and-neck cancer

Radiation treatment with intensity-modulated radiation therapy (IMRT) for head-and-neck cancer usually involves treating the superior aspects of the target volume with intensity-modulated (IM) fields, and the inferior portion of the target volume (the low neck nodes) with a static anterior-posterior field (commonly known as the low anterior neck, or LAN field). A match line between the IM and the LAN fields is created with possibly large dose inhomogeneities, which are clinically undesirable. We propose a practical method to properly match these fields with minimal dependence on patient setup errors. The method requires mono-isocentric setup of the IM and LAN fields with half-beam blocks as defined by the asymmetric jaws. The inferior jaws of the IM fields, which extend ∼1 cm inferiorly past the isocenter, are changed manually before patient treatment, so that they match the superior jaw of the LAN field at the isocenter. The matching of these fields therefore does not depend on the particular treatment plan of IMRT and depends only on the matching of the asymmetric jaws. Measurements in solid water phantom were performed to verify the field-matching technique. Dose inhomogeneities of less than 5% were obtained in the match-line region. Feathering of the match line is done twice during the course of a treatment by changing the matching jaw positions superiorly at 3-mm increments each time, which further reduces the dose inhomogeneity. Compared to the method of including the lower neck nodes in the IMRT fields, the field-matching technique increases the delivery efficiency and significantly reduces the total treatment time.

A forward-planned treatment technique using multisegments in the treatment of head-and-neck cancer

Purpose To describe in detail a forward-planned multisegment technique (FPMS) as an alternative treatment method for patients who are not suitable for inverse-planned intensity-modulated radiation therapy (IP-IMRT), or for situations where IP-IMRT is not available in a medical clinic. Methods and materials Between April 1995 and February 2002, 38 primary head-and-neck patients were treated using the FPMS technique, which has evolved over the past 7 years at our medical center. In the most recent version of the FPMS technique, which includes 5 patients examined in this analysis, the primary tumor and the upper neck nodes were treated with 7 gantry angles, including an anterior, 2 lateral, 2 anterior oblique, and 2 posterior oblique beams with a total of 13 beam shapes formed by multileaf collimators (MLC), called MLC segments. The shape of each MLC segment was carefully designed, and the associated weights were optimized through manual iterations. The lower neck nodes and the supraclavicular nodes were treated with a split-beam anterior field, matched to the inferior border of the FPMS plan at the isocenter. With an autosequencing delivery system, all fields, including dynamic wedges, can be automatically treated. The dosimetric accuracy of this technique was verified with a phantom plan and measured with an ionization chamber, as well as film dosimetry. A sample FPMS plan is described in detail, and the average results for the 5 patients treated with FPMS are retrospectively compared to results for similar patients treated with IP-IMRT. Results The gross tumor volume was prescribed to 70 Gy (2.12 Gy/fraction) at the 88% isodose line, whereas the clinical target volume received a dose of 59.4 Gy (1.8 Gy/fraction) at the 75% isodose line. The maximum dose to the brainstem and spinal cord was below 54 and 45 Gy, respectively, comparable to IP-IMRT. The mean dose to the parotid glands was 32 Gy with FPMS vs. 26 Gy with IP-IMRT. Average delivery time was shorter for FPMS (15 min) than IP-IMRT (30 min), whereas the planning time depended on the expertise of the planner. Dosimetric accuracy for FPMS and IP-IMRT plans using phantom measurements was similar, within 1% of the phantom plan. With a median follow-up of 31 months, there was no local-regional recurrence, and the incidence of xerostomia is reduced compared to conventional techniques. Conclusion FPMS achieved plans comparable to those for IP-IMRT and is an ideal alternative treatment technique for a center without the capabilities of IP-IMRT or for a patient who is not a suitable candidate, because of prolonged treatment time. The treatment outcomes from our clinical experience indicate that FPMS can achieve excellent local freedom from progression rates without causing excessive toxicity. Lastly, IP-IMRT plans should be comparable to, if not better than, FPMS plans in the treatment of head-and-neck cancer.

Cervical Metastasis of Unknown Origin: A Series of 72 Patients

Cervical metastasis of unknown origin is still a challenging problem because of its relatively poor prognosis and the uncertainty regarding the primary site. We analyzed retrospectively all 72 patients with cervical metastases of unknown origin, diagnosed and treated between 1985 and 1995 in the five university hospitals of Finland in order to analyze survival rates and some prognostic and clinical factors of the disease. The most common sites where the primary tumor was found during follow-up or at autopsy were the lung (8%), the oral and pharyngeal region (7%) and the skin (6%). When the lower neck nodes (regions IV-VI) were affected, the primary tumor was significantly ( p <0.001) more often found from the subclavicular sites. The disease-specific 5-year survival rate was 32%. In multivariate analysis, nodal stage N2c or N3 [adjusted relative hazard of death (HR) 2.43], other metastases found at the time of treatment (HR 2.15) and age>65 years (HR 2.12) were significantly associated with a poor prognosis. Median survival tended to be longer for patients treated with surgery combined with radiotherapy (39.9 months) compared with those treated with radiotherapy alone (16.8 months), but this difference was not statistically significant ( p =0.153).

Analysis of risk factors predictive of distant failure after targeted chemoradiation for advanced head and neck cancer.

Distant metastasis (DM) is the most common mode of recurrence among patients with advanced head and neck carcinoma treated with intra-arterial cisplatin and radiotherapy (RADPLAT). To identify which patients are at greatest risk for DM and would benefit the most from new strategies designed to treat occult metastases. Between 1993 and 1999, 250 patients with advanced head and neck cancer were treated by RADPLAT. Excluded from the analysis were 10 patients who either did not complete the protocol or were unavailable for follow-up and 39 patients with persistent disease or local recurrence. The incidence and the risk factors for DM in these patients were evaluated in a model that included the following factors: age, T and N classification, site of tumor, histologic grade, number (0, 1, or >1) and position (high vs low) of neck levels involved, and bilateral nodal disease. Multiple stepwise logistic regression was used for the analysis. In a univariate analysis, the following variables correlated to DM: N classification (P =.02), site of tumor (P =.01), lower neck nodes (P =.002), number of neck levels involved (P =.001), and bilateral nodal disease (P =.02). In a multivariate analysis, the most significant risk factors for DM were the number of neck levels involved and the site of the primary tumor (P<.001). The highest odds ratios for DM were among patients with multiple levels of nodal involvement (3.17) and patients with hypopharyngeal carcinoma (2.8). Patients with more than 1 level of clinical nodal involvement and patients with hypopharyngeal carcinoma have the highest risk of developing DM as the initial site of failure and would benefit most from treatment strategies that address occult distant disease.

Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy

Purpose: To report the initial experience in the definitive treatment of head and neck carcinomas using SMART (Simultaneous Modulated Accelerated Radiation Therapy) boost technique. Radiation was delivered via IMRT (Intensity Modulated Radiotherapy). The following parameters were evaluated: acute toxicity, initial tumor response, clinical feasibility, dosimetry and cost. Methods and Materials: Between January 1996 and December 1997, 20 patients with primary head and neck carcinomas were treated with SMART boost technique. The treatment fields encompassed two simultaneous targets. The primary target included palpable and visible disease sites. The secondary target included regions at risk for microscopic disease. Daily fractions of 2.4 Gy and 2 Gy were prescribed and delivered to the primary and secondary targets to a total dose of 60 Gy and 50 Gy, respectively. Lower neck nodes were treated with a single conventional anterior portal. This fractionation schedule was completed in 5 weeks with 5 daily fractions weekly. Toxicity was evaluated by RTOG acute toxicity grading criteria, evidence of infection at immobilization screw sites, subjective salivary function, weight loss, and the need for treatment split. Mean follow-up was 15.2 months. Initial tumor response was assessed by clinical and radiographical examinations. Clinical feasibility was evaluated by the criteria: time to treat patient, immobilization, and treatment planning and QA time. In dosimetry, we evaluated the mean doses of both targets and normal tissues and percent targets’ volume below goal. To evaluate cost, Medicare allowable charge for SMART boost was compared to those of conventional fractionated and accelerated radiotherapy. Results: Acute toxicity: None of the patients had a screw site infection and all patients healed well after completion of radiotherapy. Sixteen of 20 patients (80%) completed the treatment within 40 days without any split. Sixteen patients (80%) had RTOG Grade 3 mucositis while 10 patients (50%) had Grade 3 pharyngitis. Three of 20 patients (15%) had weight loss greater than 10% of their pretreatment weight. Ten patients (50%) required intravenous fluids, tube feeding or both. Nine patients (45%) reported moderate xerostomia with significant relief reported within 6 months. Initial tumor response: 19 patients (95%) had complete response (CR) while one had partial response (PR). The patient with PR had stable disease on imaging at 12 months follow-up. Two patients were found to have lung metastases at 2 months and 5 months follow-up. To date, there have been two local recurrences in the complete responders. Both patients had nasopharyngeal primary; one was retreated with radioactive Cesium-137 implant and the other died from the disease. Clinical feasibility: The average treatment time for a three-arc treatment was 17.5 minutes and 2.5 minutes for each additional arc. Eleven patients (55%) had four-arc treatment while six patients (30%) had five-arc treatment and three patients (15%) had three-arc treatment. Immobilization was reproducible within less than 2 mm. The treatment planning, QA and documentation prior to treatment averaged 2 days. Dosimetry: The mean doses to the primary and secondary targets were 64.4 Gy and 54.4 Gy, respectively; 8.9% of the primary target volume and 11.6% of the secondary target volume were below prescribed dose goal. The mean dose delivered to the mandible was 30 Gy, spinal cord 17 Gy, ipsilateral parotid 23 Gy, and contralateral parotid 21 Gy. Cost: Total Medicare allowable charge for SMART boost was $7000 compared to $8600 (conventional ) and $9400 (accelerated fractionation). Conclusions: SMART boost technique is an accelerated radiotherapy scheme that can be delivered with acceptable toxicity. It allows parotid sparing as evidenced both clinically and by dosimetry. Initial tumor response has been encouraging. It is clinically feasible and cost saving. A larger population of patients and a long-term follow-up are warranted to evaluate ultimate tumor control and late toxicity.

Treatment of nasopharyngeal carcinoma: state of the art and new perspectives (review).

The role of radiotherapy and the current strategies to improve outcome in nasopharyngeal carcinoma are reviewed. Emphasis is on the factors, which may provide a more accurate selection of patients for more aggressive treatments. Clinical data suggest that local failure and distant metastases are separate events. Thus, strategies to optimize one of them are not expected to impact significantly on the other. Patients with advanced T stage disease, cranial nerve palsy, bulky primary lesions and well differentiated tumors may benefit from more local aggressive treatment. These include higher dose radiotherapy throughout conformal 3D radiotherapy and brachytherapy. Altered fractionation schedules and concomitant chemotherapy may also enhance the results obtained by conventional external beam radiotherapy. Patients with advanced neck disease and/or low neck nodes are candidates for additional systemic treatments as well. The role of technical innovations in radiotherapy delivery and that of altered fractionation schedules are unknown, even if results from phase II studies are promising. Regarding chemotherapy, <first generation trials> have shown some impact of chemotherapy on outcome. However, additional testing is needed in order to improve the therapeutic index and validate its rationale.

Transmission Blocks for Lower Neck and Inguinal Lymph Node Radiotherapy

We evaluate techniques for radiotherapy to low neck and inguinal lymph nodes. Partial transmission blocks (PTBs) simplify treatment planning, daily setup, and improve reproducibility and dose homogeneity. PTBs minimize the risk for dose misadministration to critical organs. Disadvantages include doses that are potentially lower to the medial cervical lymphatics and higher to the femur. PTBs can surmount common treatment planning problems.

Metastasis to neck from unknown primary tumor.

The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance.