Nodal Control Rates Research Articles

Whether individualized dose escalation should be recommended for lymph nodes with different sizes in the definitive radiotherapy of cervical cancer?

Background and purposeDose escalation for positive node maybe improve the regional control of patients with node-positive cervical cancer, but the optimal dose for nodes of different sizes remains controversial. The purpose of this study was to explore the individualized dose escalation for lymph nodes (LNs) with different sizes in the definitive radiotherapy of cervical cancer.MethodsA total of 1002 cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB1–IVA, who were treated by definitively radiotherapy between September 2013 and December 2016 were enrolled. All LNs identified by computed tomography/magnetic resonance imaging (CT/MRI) were assigned into three groups according to the short diameters of < 1 cm, 1–2 cm or ≥ 2 cm at pretreatment.ResultsIn total, 580 patients with 1310 LNs were detected. The nodal control rate in groups of LNs < 1 cm, 1–2 cm and ≥ 2 cm was 99.4%, 96%, and 75.9%, respectively (P = 0.000). Among LNs < 1 cm, the control, overall survival (OS) and progression-free survival (PFS) rates did not significantly differ among three dose-based groups (≤ 50.4 Gy, 50.4–60 Gy, > 60 Gy) (control rate, 99.4% vs. 99.3% vs. 100%, P = 0.647) (5-year OS, 76.2% vs. 79% vs. 81.6%, P = 0.682) (5-year PFS, 74.1% vs. 73.9% vs. 78.9% P = 0.713). Among LNs of 1–2 cm, the control and PFS rates were significantly higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy (control rate, 98% vs. 93.6%, P = 0.028) (5-year PFS, 69.6% vs. 56.7%, P = 0.025). However, this did not cause a significant difference for 5-year OS rate (72.6% vs. 68.3%, P = 0.5). Among LNs ≥ 2 cm, the control, OS, and PFS rates were higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy, while no significant difference was found (control rate, 82.1% vs. 63.2%, P = 0.107) (5-year OS, 60.6% vs. 37.5%, P = 0.141) (5-year PFS, 51.5% vs.37.5%, P = 0.232).ConclusionsRadiation dose escalation is not necessary for LNs < 1 cm, and dose escalation of 55 Gy is enough for LNs of 1–2 cm.

Pattern of relapse in pediatric localized extremity rhabdomyosarcomas correlated with locoregional therapies administered.

Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered. All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging. We identified 59patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32patients (54%) and modified the lymph node stage in 8of the 59patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26patients underwent complete tumor resection, 17had R1 margins, and 5were not operated due to early tumor progression. With amedian follow-up of 82months (range: 5-287), 18relapses had occurred, at least locoregional in 12cases. The 5‑year local and nodal control rates were 73% (63-86%) and 86% (77-95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45-72%]) and 70% (95%CI [58-84%]), respectively. The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.

Involved-Field Irradiation in Definitive Chemoradiotherapy for Locoregional Esophageal Squamous Cell Carcinoma: Results From the ESO-Shanghai 1 Trial.

To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy

AimsThere are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. Materials and methodsPatients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4–6 Gy sequential boost for nodes >2 cm. ResultsOf the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9–46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). ConclusionThis is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Dose Response Relationship and Prognostic Factors of Nodal Control Rate of Metastatic Lymph Nodes in Cervical Cancer

In contrast to excellent local control in definitive aim radiation therapy (RT) of cervical cancer, control rate of metastatic lymph nodes remains insufficient. Therefore, radiation boost to metastatic lymph nodes has been attempted, but little is known about the optimal dose and prognostic factors of regional nodal control. In this study, we retrospectively investigated the dose response relationship of metastatic lymph nodes as well as prognostic factors of nodal control, and attempted to propose optimal dose for individual metastatic lymph nodes. We identified 90 patients (295 lymph nodes) who received definitive aim RT for node positive cervical cancer between 2013 and 2017. Total prescribed dose to each metastatic lymph node was converted to 2 Gy equivalent dose (EQD2, α/β = 10 Gy). Each node was tracked individually from initial diagnosis to any recurrence in the same specific node. Any tumor or treatment factors predictive of nodal control were searched. In addition, we attempted to stratify risk groups in order to find optimal dose for nodal control in a certain risk group. The median number of metastatic lymph nodes per patient was 2 (range, 1-14). Regarding total lymph nodes, the most common pathology was squamous cell carcinoma (85.6%) followed by adenocarcinoma (8.9%) and others (5.6%). The mean nodal volume at initial diagnosis was 5.0 ± 9.2 mL, and the mean total prescribed dose in EQD2 for each node was 55.0 ± 6.8 Gy. With median follow up of 25 months (range, 3-57 months), 32 nodal failures occurred, and 2-year nodal control rate was 89%. In multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) higher than 3.0 (p<0.001), para-aortic nodes (vs. pelvic nodes, p=0.013), larger initial nodal volume (p<0.001) and lower total dose (HR 0.90 for increase of 1 Gy in EQD2; 95% CI 0.85-0.95; p<0.001) were identified as risk factors for poor nodal control. Each node was stratified into two risk groups; low risk group with none or one risk factor, and high risk group with two or three risk factors. For risk group analysis, initial nodal volume was dichotomized (≤ 5.3 mL or > 5.3 mL). ROC curve analysis showed that 53.1 Gy and 62.0 Gy was the optimal cut-off dose for predicting nodal control rate in low and high risk group, respectively. In low risk group, doses higher than 53.1 Gy showed significantly superior nodal control rate (p=0.050) with 2-year nodal control rate of 99% (vs. 93% for ≤ 53.1 Gy). In high risk group, doses equal to or higher than 62.0 Gy showed superior nodal control rate with marginal significance (p=0.053) with 2-year nodal control rate of 80% (vs. 62% for < 62.0 Gy). Our data demonstrated that nodal control depends on the prescribed dose to lymph node, NLR, location of lymph node, and initial nodal volume. Therefore, these factors should be considered to enhance nodal control at the stage of treatment plan.

Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study

IntroductionPatients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation. MethodsThis retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015. ResultsOf 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography–computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival. ConclusionBilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.

Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies

AimsTo determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP). Materials and methodsA single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension. ResultsThirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4–100) and 89.8% (78.4–100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%. ConclusionsAt a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes.

High-dose-rate interstitial brachytherapy in early stage oral tongue cancer - 15 year experience from a tertiary care institute.

PurposeTo determine outcomes of interstitial high-dose-rate brachytherapy (HDR-BT) in patients with early stage oral tongue cancer.Material and methodsNinety-two patients with stage I and II oral tongue cancer were treated with HDR-BT between 1999 and 2014: brachytherapy alone = 62 (67.4%), and combination of external beam radiotherapy (EBRT) and brachytherapy = 30 (32.6%). Median follow-up was 53.5 months. Patterns of failure, overall survival (OS), disease-free survival (DFS), local control rates (LCR), and nodal control rates (NCR) were determined.Results5-year OS, DFS, LCR, and NCR were 73.2%, 58.2%, 64.2%, and 83.8%, respectively. In total, 43 patients (46.7%) failed treatment: isolated local failures = 28 (30.4%), isolated nodal failures = 8 (8.7%), both local and regional failures = 7 (7.6%). While in T1 stage, 5 year LCR were significantly higher in brachytherapy alone group compared to combined EBRT and brachytherapy group (81.7% vs. 62.5%, p = 0.04), the isolated nodal failure rates were not significantly different among the two groups. For T2 stage, NCR were higher in combined EBRT and brachytherapy group compared to brachytherapy alone (92.9% vs. 74.3%). Acute mucositis (grade ≥ 2) was seen more in brachytherapy alone group compared to the combined modality group (87% vs. 66%), and this correlated significantly with the higher biological equivalent dose (BED) in the brachytherapy alone group.ConclusionsOur study recommends treating patients with brachytherapy alone in T1 stage, and demonstrates the need for addressing nodal region either by neck dissection or nodal irradiation in T2 stage patients. Also, the study highlights the need for dose escalation (from the doses used in the study) in both T1 and T2 stage tumors when using interstitial brachytherapy either as sole modality or as a boost.

Evaluation of a 36 Gy elective node irradiation dose in anal cancer

PurposeTo retrospectively analyze the efficacy of 36Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme. Methods and materialsBetween January1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4weeks followed after a 2-week gap by a boost dose of 23.4Gy over 17days to the macroscopic disease. Mitomycin C combined with fluorouracil, capecitabin or cisplatin was given at day 1 of each sequence of RT. ResultsDisease stages were I: 3, II: 78, IIIA: 23, IIIB: 38. Compliance rates were 97.2% with RT and 87.9% with chemotherapy. After a median follow up of 48months [3.6–192], estimated 5-year overall survival and colostomy-free survival were 75.4% and 85.3% respectively. Eleven patients (7.7%) never achieved a complete response, 15 had a local component of recurrence and 5 a regional one. One patient had failure in the common iliac node area outside the treatment fields. The inguinal control rate was 98.5%. The 5-year tumor and nodal control rates were 81.5% and 96.0%, respectively. ConclusionChemoradiation with a dose of 36Gy ENI achieved excellent nodal control. However, it is necessary to improve the 5-year control rate of the primary tumor. Omitting the gap and using additional doses per fraction or hyper-fractionation are to be explored.

Less may be more: nodal treatment in neck positive head neck cancer patients.

Ongoing debates about the need and extent of planned neck dissection (PND), and required nodal radiation doses volumes lead to this evaluation. Aim was to assess nodal control after definitive intensity modulated radiation therapy (IMRT ± systemic therapy) followed by PND in our head neck cancer cohort with advanced nodal disease. Between 01/2005 and 12/2013, 99 squamous cell cancer HNC patients with pre-therapeutic nodal metastasis ≥3 cm were treated with definitive IMRT followed by PND. In addition, outcome in 103 patients with nodal relapse after IMRT and observation only (no-PND cohort) were analyzed. Prior to PND, PET–CT, fine needle aspirations, ultrasound and palpation were assessed regarding its predictive value. Patterns of nodal relapse were assessed in patients with isolated neck failure after definitive IMRT alone. 70/99 (70 %) PND specimens showed histopathological complete response (hCR), which translated into statistically significantly superior survival compared with partial response (hPR) with 4-year overall survival, disease specific survival and nodal control rates of 90/83/96 vs 67/60/78 % (p = 0.002/0.001/0.003). 1/99 patient developed isolated subsequent nodal disease. 64/2147 removed nodes contained viable tumor (3 %). Predictive information of the performed diagnostic investigations was not reliable. 17/70 hCR patients showed true negative findings in available three to four investigations (0/29 hPR). 27/103 no-PND patients developed isolated neck disease (26 %) with successful salvage in 21/24 [88 %, or 21/27 (78 %)]. Nearly all failures occurred in the prior nodal gross tumor volume area. A more restrictive approach regarding PND and/or nodal IMRT dose-volumes may be justified.

Outcomes of routine ilioinguinal lymph node dissection for palpable inguinal melanoma nodal metastasis.

Patients who present with palpable inguinal melanoma nodal metastasis have two surgical options: inguinal or ilioinguinal lymph node dissection. Indications for either operation remain controversial. This study examined survival and recurrence outcomes following ilioinguinal dissection for patients with palpable inguinal nodal metastasis, and assessed the incidence and preoperative predictors of pelvic nodal metastasis. This was a retrospective clinicopathological analysis of consecutive surgical patients with stage III malignant melanoma. All patients underwent a standardized ilioinguinal dissection at a specialist tertiary oncology hospital over a 12-year period (1998-2010). Some 38.9 per cent of 113 patients had metastatic pelvic nodes. Over a median follow-up of 31 months, the 5-year overall survival rate was 28 per cent for patients with metastatic inguinal and pelvic nodes, and 51 per cent for those with inguinal nodal metastasis only (P = 0.002). The nodal basin control rate was 88.5 per cent. Despite no evidence of pelvic node involvement on preoperative computed tomography (CT), six patients (5.3 per cent) with a single metastatic inguinal lymph node had metastatic pelvic lymph nodes. Logistic regression analysis showed that the number of metastatic inguinal nodes (odds ratio 1.56; P = 0.021) and suspicious CT findings (odds ratio 9.89; P = 0.001) were both significantly associated with metastatic pelvic nodes. The specificity of CT was good (89.2 per cent) in detecting metastatic pelvic nodes, but the sensitivity was limited (57.9 per cent). Metastatic pelvic nodes are common when palpable metastatic inguinal nodes are present. Long-term survival can be achieved following their resection by ilioinguinal dissection. As metastatic pelvic nodes cannot be diagnosed reliably by preoperative CT, patients presenting with palpable inguinal nodal metastasis should be considered for ilioinguinal dissection.

Locoregional Control After Intensity-modulated Radiotherapy for Nasopharyngeal Carcinoma with an Anatomy-based Target Definition

The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Selective use of postoperative neck radiotherapy in oral cavity and oropharynx cancer: a prospective clinical study

BackgroundIn cervical postoperative radiotherapy, the target volume is usually the same as the extension of the previous dissection. We evaluated a protocol of selective irradiation according to the risk estimated for each dissected lymph node level.MethodsEighty patients with oral/oropharyngeal cancer were included in this prospective clinical study between 2005 and 2008. Patients underwent surgery of the primary tumor and cervical dissection, with identification of positive nodal levels, followed by selective postoperative radiotherapy. Three types of selective nodal clinical target volume (CTV) were defined: CTV0, CTV1, and CTV2, with a subclinical disease risk of <10%, 10-25%, and 25% and a prescribed radiation dose of <35 Gy, 50 Gy, and 66–70 Gy, respectively. The localization of node failure was categorized as field, marginal, or outside the irradiated field.ResultsA consistent pattern of cervical infiltration was observed in 97% of positive dissections. Lymph node failure occurred within a high-risk irradiated area (CTV1-CTV2) in 12 patients, marginal area (CTV1/CTVO) in 1 patient, and non-irradiated low-risk area (CTV0) in 2 patients. The volume of selective lymph node irradiation was below the standard radiation volume in 33 patients (mean of 118.6 cc per patient). This decrease in irradiated volume was associated with greater treatment compliance and reduced secondary toxicity. The three-year actuarial nodal control rate was 80%.ConclusionThis selective postoperative neck irradiation protocol was associated with a similar failure pattern to that observed after standard neck irradiation and achieved a significant reduction in target volume and secondary toxicity.

Outcomes of Patients With Head-and-Neck Cancer of Unknown Primary Origin Treated With Intensity-Modulated Radiotherapy

To analyze survival, failure patterns, and toxicity in patients with head-and-neck carcinoma of unknown primary origin (HNCUP) treated with intensity-modulated radiotherapy (IMRT). Records from 27 patients with HNCUP treated during the period 2002-2008 with IMRT were reviewed retrospectively. Nodal staging ranged from N1 to N3. The mean preoperative dose to gross or suspected disease, Waldeyer's ring, and uninvolved bilateral cervical nodes was 59.4, 53.5, and 51.0 Gy, respectively. Sixteen patients underwent neck dissection after radiation and 4 patients before radiation. Eight patients with advanced nodal disease (N2b-c, N3) or extracapsular extension received chemotherapy. With a median follow-up of 41.9 months (range, 25.3-93.9 months) for non deceased patients, the 5-year actuarial overall survival, disease-free survival, and nodal control rates were 70.9%, 85.2%, and 88.5%, respectively. Actuarial disease-free survival rates for N1, N2, and N3 disease were 100%, 94.1%, and 50.0%, respectively, at 5 years. When stratified by non advanced (N1, N2a nodal disease without extracapsular spread) vs. advanced nodal disease (N2b, N2c, N3), the 5-year actuarial disease-free survival rate for the non advanced nodal disease group was 100%, whereas for the advanced nodal disease group it was significantly lower at 66.7% (p = 0.017). Three nodal recurrences were observed: in 1 patient with bulky N2b disease and 2 in patients with N3 disease. No nodal failures occurred in patients with N1 or N2a disease who received only radiation and surgery. Definitive IMRT to 50-56 Gy followed by neck dissection results in excellent nodal control and overall and disease-free survival, with acceptable toxicity for patients with T0N1 or non bulky T0N2a disease without extracapsular spread. Patients with extracapsular spread, advanced N2 disease, or N3 disease may benefit from concurrent chemotherapy, targeted therapeutic agents, or accelerated radiation regimens in addition to surgery.

Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

Background Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. Methods We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Results Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Conclusions Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.

Surviving Hypopharynx–Larynx Carcinoma in the Era of IMRT

Outcome in locoregionally advanced laryngeal carcinoma and hypopharyngeal carcinoma after conventional radiation techniques is known for modest disease control and considerable late toxicity. Considering the lack of standardization in prescription dose for intensity-modulated radiotherapy (IMRT), we aimed to compare the results after our methods of simultaneously integrated boost IMRT with published results. Between March 2002 and December 2008, 65 hypopharyngeal, 31 supraglottic, and 27 locoregionally advanced glottic tumor patients underwent definitive IMRT (with simultaneous chemotherapy in 86%). Of these, 64% presented with locoregionally advanced disease. Mean follow-up was 26 months (range, 3-83 months), with a median of 21 months. Treatment (2.0-2.2 Gy per fraction, 66-72.6 Gy) followed a prospectively defined protocol. If the boost volume included more than half of the larynx or a substantial part of the pharynx, dose was limited to 2.0 Gy per fraction. The 2-year local, nodal, and locoregional control (LRC) rates for the entire cohort were 82%, 90%, and 77%, respectively; the disease-free and overall survival rates were 75% and 83%, respectively. The ultimate 2-year LRC rate, including salvage surgery, was 86%. Laryngectomy was required in 2 LRC patients needing tracheostoma already before; 2 further LRC patients needed tracheostomy before IMRT and remained tracheostoma dependent, and 3 patients remained feeding tube dependent after IMRT. Salvage laryngectomy was successful in 8 of 11. Of all 123 patients, 91 patients (74%) are locoregionally controlled and live with a functional laryngopharynx. Simultaneously integrated boost IMRT with limited acceptance of dose inhomogeneity resulted in very satisfactory disease control despite a slight left shift of planning target volume curves on the dose-volume histogram. Considering the treatment tolerance, a careful increase in dose in our patients seems possible. Dose-volume comparisons remain difficult because no international standards have been defined for contouring and volume-related dose distribution.

Carcinoma of the nasal cavity and paranasal sinuses in Denmark 1995–2004

Objective. To evaluate the treatment outcome for sino-nasal carcinomas in Denmark from 1995–2004 and compare the results to the previous Danish survey covering 1982–1991. Design. Retrospective follow-up. Materials and methods. In the five Danish head and neck oncology centres, charts of all consecutive patients with sino-nasal carcinomas were reviewed and data extracted to a common database. Altogether 242 patients from the period 1995–2004 were identified. Of these 162 (67%) were male and 80 (33%) female. Histologies included squamous cell carcinoma (55%), adenocarcinoma (28.5%), adenoid-cystic carcinoma (5.0%), undifferentiated carcinoma (4.5%), transitiocellular carcinoma (1.7%), mucoepidermoid carcinoma (0.8%), neuroendocrine carcinoma (2.5%), small cell carcinomas (1.2%) and carcinomas not otherwise specified (0.8%). Treatments included radiotherapy alone 79 (33%), surgery alone 29 (12%), combined surgery and radiotherapy 96 (40%), palliative/no treatment 38 (16%). A total of 204 (86%) patients were treated with curative intent. Results. Of the 204 patients treated with curative intent, 94 (46%) relapsed. Most failures were in T-site (63, 30%). N-site failures were 10 (5%) and M-site failures six (3%). Failure occurring in T+N-site, T+M-site, N+M-site and T+N+M-site were seven (3%), two (1%), one (0.5%) and five (3%) respectively. The 5-year actuarial local, nodal and loco-regional control rates were 55±4%, 86±3%, 49±4%, respectively. The overall 5-year actuarial survival rate for the entire cohort was 47±3%, and the corresponding cancer-specific 5-year actuarial survival rate was 57±3%. Female gender, nasal cavity tumour, adenocarcinoma and low clinical stage were significant positive prognostic factors in univariate analysis. A Cox multivariate analysis showed that only tumour site and clinical stage were independent significant prognostic factors. Conclusion. The current series has confirmed stage and tumour site as independent prognostic factors. Compared to the previous Danish survey covering the period 1982–1991, the overall survival and cancer-specific survival rates have improved significantly.

Outcome in recurrent head neck cancer treated with salvage-IMRT

BackgroundRecurrent head neck cancer (rHNC) is a known unfavourable prognostic condition.The purpose of this work was to analyse our rHNC subgroup treated with salvage-intensity modulated radiation therapy (IMRT) for curable recurrence after initial surgery alone.PatientsBetween 4/2003–9/2008, 44 patients with squamous cell rHNC were referred for IMRT, mean/median 33/21 (3–144) months after initial surgery. None had prior head neck radiation. 41% underwent definitive, 59% postoperative IMRT (66–72.6 Gy). 70% had simultaneous chemotherapy.MethodsRetrospective analysis of the outcome following salvage IMRT in rHNC patients was performed.ResultsAfter mean/median 25/21 months (3–67), 22/44 (50%) patients were alive with no disease; 4 (9%) were alive with disease. 18 patients (41%) died of disease. Kaplan Meier 2-year disease specific survival (DSS), disease free survival (DFS), local and nodal control rates of the cohort were 59/49/56 and 68%, respectively.Known risk factors (advanced initial pTN, marginal initial resection, multiple recurrences) showed no significant outcome differences. Risk factors and the presence of macroscopic recurrence gross tumor volume (rGTV) in oral cavity patients vs others resulted in statistically significantly lower DSS (30 vs 70% at 2 years, p = 0.03). With respect to the assessed unfavourable outcome following salvage treatment, numbers needed to treat to avoid one recurrence with initial postoperative IMRT have, in addition, been calculated.ConclusionA low salvage rate of only ~50% at 2 years was found. Calculated numbers of patients needed to treat with postoperative radiation after initial surgery, in order to avoid recurrence and tumor-specific death, suggest a rather generous use of adjuvant irradiation, usually with simultaneous chemotherapy.

Definitive radiation therapy for squamous cell carcinoma of the soft palate

We report the University of Florida experience with soft-palate carcinoma treated with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease in the neck. A total of 145 patients treated with curative intent from 1963 to 2004 were included. Potential follow-up was > or =2 years. Local control rates at 5 years were: T1, 90%; T2, 91%; T3, 67%; T4, 57%. Nodal control rates at 5 years were: N0, 90%; N1, 82%; N2, 68%; N3, 71%. Ultimate local-regional control rates at 5 years were: stage I, 89%; stage II, 88%; stage III, 96%; stage IVA, 63%; stage IVB, 43%. In multivariate analysis, overall treatment time significantly affected local and ultimate local-regional control, and nodal stage significantly affected overall survival. Overall survival rate at 5 years was 44%. Cause-specific survival rate at 5 years was 73%. The likelihood of cure after definitive radiotherapy is relatively high and is impacted by disease extent and overall treatment time.

Radiographic Complete Response on Post Treatment CT Imaging Eliminates the Need for Adjuvant Neck Dissection After Treatment for Node Positive Head and Neck Cancer

The primary purpose of this study was to correlate radiographic response in the neck to clinical outcomes for patients with node positive head and neck cancer. One hundred three patients with stage III/IV node positive cancer were treated with definitive radiotherapy or chemoradiation at a single institution from 1990 to 2004. Follow-up ranged from 8 months to 144 months with a median of 42 months. Posttreatment CT scans were called complete radiographic response (rCR) or partial radiographic response. Actuarial 36 month rates of survival, control above the clavicles, and nodal control were 66%, 74%, and 90%, respectively. Patients, who had rCR on posttreatment CT scan, who had a neck dissection had a nodal control rate of 94% compared with those without neck dissection of 97%. Patients with partial radiographic response who were treated with neck dissection had a nodal control rate of 94% compared with those without neck dissection of 73%. Based on this data, there was no suggestion that neck dissection improved outcome for patients with rCR on posttreatment imaging 4 to 6 weeks after radiation.