Case report: Giant lymph node metastases: a new opportunity for cancer radioimmunotherapy?

Background: Despite the significant progress made in radiotherapy and chemotherapy for the treatment of cervical cancer, patients with lymph node metastasis still have a poor prognosis. It is widely accepted that lymph node metastasis plays a crucial role in the spread of cancer to other organs and is considered an independent factor in predicting a poor prognosis. However, recent research suggests that the importance of lymph nodes in tumor therapy needs to be reevaluated, as preserving the integrity of lymph nodes before immunotherapy can enhance treatment effectiveness. Case presentation: In this report, we present two cases of advanced cervical cancer patients with giant metastatic lymph node lesions in the neck. These patients were effectively treated with a combination of local radiotherapy and immunotherapy after conventional chemoradiotherapy had failed. The combination therapy resulted in significant clinical improvements, with patient 1 achieving over 12 months of progression-free survival (PFS) and patient 2 maintaining sustained remission for an impressive 24 months. Conclusions: The combination of local radiotherapy and immunotherapy shows promise as a viable treatment option for cervical cancer patients with distant lymph node metastasis, and the giant lymph node metastases may play an important role in this process, which might provide a new opportunity for cancer radioimmunotherapy.

A retrospective study on improving the accuracy of radiotherapy for patients with breast cancer with lymph node metastasis using Styrofoam.

BACKGROUND: To retrospectively analyze the accuracy of radiotherapy using cone beam computed tomography (CBCT), Styrofoam fixation, and breast bracket fixation in the chest wall target area and supraclavicular lymphatic drainage area (supraclavicular target area) of patients with breast cancer.and compare the setting efficiency and comfort satisfaction. PATIENTS AND METHODS: A total of 65 patients with postoperative lymphatic metastasis of breast cancer, including 36 cases of Styrofoam fixation and 29 cases of breast bracket fixation, were recruited from March 2021 to August 2022 and retrospectively analyzed. All the patients underwent CBCT scans weekly, and the setup errors of the chest wall and supraclavicular target volume were compared and recorded. The planning target volume (PTV) margins of the two groups were calculated using the correlation MPTV = 2.5Σ + 0.7σ. The setup time and comfort satisfaction scores of the two groups were recorded and analyzed. The correlations among errors in each direction were analyzed using the Pearson correlation analysis. RESULTS: There was a significant difference in the left-right direction (X) axis of the chest wall target area between the Styrofoam and breast bracket groups (1.59 ± 1.47 mm vs. 2.05 ± 1.64 mm, P = 0.012). There were statistical differences in the ventrodorsal direction (Z) and bed angle of the supraclavicular target area, the data were (1.36 ± 1.27 mm vs. 1.75 ± 1.55 mm, P = 0.046; 0.47 ± 0.47° vs. 0.66 ± 0.59°, P = 0.006, respectively). In the X, Y, and Z directions, the respective PTV margins of the two groups in the chest wall target area were 5.01 mm, 5.99 mm, and 5.47 mm in the Styrofoam group, while those in the breast bracket group were 6.10 mm, 6.34 mm, and 6.10 mm, respectively. Moreover, the PTV margins of the supraclavicular target in the three directions were 3.69 mm, 3.86 mm, and 4.28 mm in the Styrofoam group, while those in the breast bracket group were 3.99 mm, 3.72 mm, and 5.45 mm, respectively. The setup time of the two groups was 3.4 ± 1.1 min and 5.5 ± 3.1 min (P = 0.007). The subjective comfort satisfaction scores of the two groups were 27.50 ± 1.24 and 25.44 ± 1.23 (P < 0.001). CONCLUSIONS: The application of Styrofoam fixation in radiotherapy of breast cancer in the supraclavicular lymph node area has several advantages as compared to breast bracket fixation, including higher positioning accuracy, smaller external expansion boundary, improved work efficiency, and patients' comfort, which might provide a reference for clinical work.

Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial.

BACKGROUND: Current radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes of the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden. METHODS: ISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 414 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution scale and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs. DISCUSSION: The results of this trial are expected to confirm that ISI is a non-inferior strategy to ERI in stage I-III patients with low LN burden, enabling the minimization of treatment-related toxicity and improvement of long-term QoL without compromising regional control. TRIAL REGISTRATION: ClinicalTrails.gov, NCT05145660. Registered December 6, 2021.

Clinical value of 125I radioactive seed implantation in the treatment of lymph node metastasis of 131I refractory differentiated thyroid cancer.

PURPOSE: To evaluate the clinical value of 1251 seed implantation in the treatment of lymph node metastasis of 111 cases of refractory differentiated thyroid cancer (RAIR-DTC). METHODS AND MATERIALS: From January 2015 to June 2016, 42 patients with RAIR-DTC with lymph node metastasis (14 males and 28 females, median age 49 years) were analyzed retrospectively. After CT-guided 1251 seed implantation, CT was reexamined 2,4,6 months after operation, and the changes of metastatic lymph node size, serum thyroglobulin (Tg) level and complications were compared before or after treatment. Paired-Samples T Test, Methods repetitive measure analysis of variance, Spearman correlation coefficient analysis were used to analyze the data. RESULTS: Among the 42 patients, 2 had complete remission (4.76%), 9 had partial remission (21.43%), 29 had no change (69.05%), and 2 had disease progression (4.76%), with an overall effective rate of 95.24% (40/42). The diameter of lymph node metastasis was (1.39 ± 0.75) cm after treatment and (1.99 ± 0.38) cm before treatment; the diameter of lymph node metastasis was significantly reduced after treatment compared with that before metastasis (t = 5.557, P< 0.01); the serum Tg at 2, 4 and 6 months after treatment were (53.34 ± 14.05) ug/L, (33.17 + 7.61)ug/L and (25.93 ± 10.91)ug/L, respectively, compared with (57.72 ± 15.23)ug/L before treatment, and the differences between serum Tg after treatment and before treatment were all statistically significant (F = 23.612,P<0.05). Except for the diameter of lymph node metastasis (χ2 = 4.524, P<0.05), the patients' age, gender, metastasis site and the number of implanted particles per lesion were not influential factors in the efficacy (χ2 = 0.569-15.884, rs = 0.277, all P>0.05). CONCLUSION: 125I RSIT can significantly alleviate the clinical symptoms of RAIR-DTC patients with LNM, and the LNM lesions size has relevance for the treatment effect. The clinical follow-up time of serum Tg level can be extended to 6 months or even longer.

Clinical treatment considerations in the intensity-modulated radiotherapy era for parotid lymph node metastasis in patients with nasopharyngeal carcinoma.

PURPOSE: No specific irradiation guidelines have been proposed for parotid lymph node (PLN) metastasis in patients with nasopharyngeal carcinoma (NPC). This study aimed to explore the dose prescription and target delineation for PLN metastasis in patients with NPC. METHODS: With the NPC database from a big-data platform, 10,685 patients with primarily diagnosed, non-distant metastatic, histologically proven NPC and treated with intensity modulated radiotherapy (IMRT) at our center from 2008 to 2019 were reviewed and those with PLN metastasis were enrolled in this study. Dosimetry parameters were collected from the dose-volume histograms (DVH). The primary endpoint was overall survival (OS). Least absolute shrinkage and selection operator regression (LASSO) was operated for variable selection. Multivariate Cox regression analysis was applied to identify the independent prognostic factors. RESULTS: PLN metastases were identified in 275/10685 (2.5%) patients. Of 367 positive PLN, 199 were in superficial intra-parotid, followed by 70 in deep intra-parotid, 54 in subparotid and 44 in subcutaneous pre-auricular. Better survival outcome was observed in PLN-radical IMRT group, compared with PLN-sparing group. In 190 patients received PLN-radical IMRT, multivariate analysis revealed that D95% of level VIII > 55 Gy was an independent beneficial prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and parotid relapse-free survival (PRFS). CONCLUSION: Based on the distribution pattern of PLN metastasis in NPC and the result of dose-finding study, involving the ipsilateral level VIII into low-risk clinical target volume (CTV2) is recommended for NPC with PLN metastasis.

Primary tumour iodine avidity in relation to uptake in persistent metastatic disease in papillary and poorly differentiated thyroid cancer.

PURPOSE: Patients with persistent or recurrent papillary and poorly differentiated thyroid cancer can be effectively treated with radioiodine, if the tumour tissue is iodine-avid. However, iodine-avidity status is often unknown at the time of initial radioiodine treatment, limiting any adaptive approach. This study aimed to clarify the relationship between pre-therapeutic iodine avidity in primary tumour tissue, initial lymph node metastases and iodine uptake in subsequent metastases. METHODS: Iodine avidity was prospectively assessed pre-therapeutically in 35 patients by injection of tracer amounts of iodine-131 two days prior to surgery. Iodine concentrations in resected tissue samples were measured, enabling accurate and histologically verifiable iodine avidity data for both primary tumour and initial lymph node metastases. Iodine uptake in persistent metastatic disease was assessed by review of radiology, and treatment response was examined through journal studies. RESULTS: Out of data from 35 patients, 10 had persistent disease at presentation or during follow-up (range 19-46 months). Four patients had non-avid persistent metastatic disease, all with low iodine avidity in their primary tumours and initial lymph node metastases. Patients with low pre-therapeutic iodine avidity did not appear to have greater risk of persistent disease. CONCLUSION: The results indicate a close link between pre-therapeutically measured iodine concentrations in primary tumours with iodine avidity of any subsequent metastases.

High grade leiomyosarcoma of the transverse colon with positive lymph node metastasis: to treat or not to treat with adjuvant radiation therapy?

Intra-abdominal leiomyosarcomas (LMSs) are aggressive malignant tumours arising from smooth muscle cells. These neoplasms are extremely rare and account for 10%-20% of primary soft tissue sarcomas and approximately 0.1% of all colorectal malignancies. Intra-abdominal LMS has a very poor prognosis with an estimated 5-year survival rate between 20% and 50% and the size of the tumour being the main determinant of prognosis. Treatment is further complicated by different anatomic variants with differing clinical behaviours impacting prognosis. Newer techniques in radiation treatment such as intensity-modulated, intraoperative electron and proton beam radiotherapies allow for cases with high probability of local recurrence or likelihood of residual microscopic disease after surgical resection to be treated with precise radiation doses to the targeted tumour volume. We present a case of high grade LMS of the distal transverse colon with positive lymph node metastasis treated by surgical excision followed by adjuvant radiotherapy and discuss the current role of radiotherapy.

Multi-institutional Development and Validation of Contouring Guidelines for Para-aortic Elective Nodal Irradiation in Prostate Cancer Based on Patterns of Involvement on Targeted Molecular Imaging Positron Emission Tomography/Computed Tomography.

PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.

Stereotactic body radiotherapy for mediastinal lymph node with CyberKnife®: Efficacy and toxicity.

PUPRPOSE: Stereotactic body radiotherapy is more and more used for treatment of oligometastatic mediastinal lymph nodes. The objective of this single-centre study was to evaluate its efficacy in patients with either a locoregional recurrence of a pulmonary or oesophageal cancer or with distant metastases of extrathoracic tumours. PATIENTS AND METHODS: Patients with oligometastatic mediastinal lymph nodes treated with CyberKnife from June 2010 to September 2020 were screened. The primary endpoint was to assess local progression free survival and induced toxicity. Secondary endpoints were overall survival and progression free survival. The delay before introduction of systemic treatment in the subgroup of patients who did not receive systemic therapy for previous progression was also evaluated. RESULTS: Fifty patients were included: 15 with a locoregional progression of a thoracic primary tumour (87% pulmonary) and 35 with mediastinal metastasis of especially renal tumour (29%). Median follow-up was 27 months (6-110 months). Local progression free survival at 6, 12 and 18 months was respectively 94, 88 and 72%. The rate of local progression was significantly lower in patients who received 36Gy in six fractions (66% of the cohort) versus other treatment schemes. Two grade 1 acute oesophagitis and one late grade 2 pulmonary fibrosis were described. Overall survival at 12, 18 and 24 months was respectively 94, 85 and 82%. Median progression free survival was 13 months. Twenty-one patients were treated by stereotactic body irradiation alone without previous history of systemic treatment. Among this subgroup, 11 patients (52%) received a systemic treatment following stereotactic body radiotherapy with a median introduction time of 17 months (5-52 months) and 24% did not progress. CONCLUSION: Stereotactic body irradiation as treatment of oligometastatic mediastinal lymph nodes is a well-tolerated targeted irradiation that leads to a high control rate and delay the introduction of systemic therapy in selected patients.

Discussion on the necessity of bilateral inguinal lymphatic area irradiation for cervical cancer with invasion of the lower one-third of the vagina.

Context: According to the National Comprehensive Cancer Network guidelines for cervical cancer, patients with cervical cancer invading the lower one-third of the vagina require bilateral inguinal lymphatic area preventive irradiation. However, it is not clear whether they need preventive inguinal area irradiation. Aims: The aim of this study is to evaluate the necessity of bilateral inguinal lymphatic area irradiation for patients with cervical cancer with invasion of the lower one-third of the vagina. Settings and Design: Patients without inguinal lymph node metastasis were divided into preventive radiotherapy and nonpreventive radiotherapy groups. The occurrence of inguinal skin damage, lower extremity edema, and femoral head necrosis was observed during and after treatment. Methods and Material: In total, 184 patients with cervical cancer with invasion of the lower one-third of the vagina were selected. A trial and control method was used to select 180 patients without inguinal lymph node metastasis. Statistical Analysis: Comparison between groups was performed using a t test. Data were enumerated using frequency (percentage), and comparison between groups was performed using a Chi-square test. Results: Imaging examination revealed inguinal lymph node enlargement in 7.07% of patients, and only four cases (2.17%) were further confirmed by pathology. The inguinal lymph node metastasis rate in these patients was very low. The prophylactic irradiation group showed a high occurrence rate of side injury. In the follow-up of both groups, no recurrence was detected in the inguinal lymph nodes. Conclusions: Prophylactic irradiation of inguinal lymph nodes is not essential for patients without pathological metastasis.

[An Abscopal Effect after Palliative Radiotherapy in a Patient with a Locally and Lymph Node Recurrent Gastric Cancer].

Radiotherapy is known to have a high local effect for cancer treatment. However, several reports that radiotherapy could stimulate the anti-tumor effect by releasing endogenous signals and cytokines, increasing the presentation of tumor associated antigens on dendritic cells, and proliferating tumor antigen-specific cytotoxic T lymphocytes have been shown. A tumor regression in both non-irradiated and irradiated fields have observed, which is called"abscopal effect". We report a case of the abscopal effect in adenocarcinoma of the stomach with locally and lymph node recurrence after surgery. A 59-year-old Japanese male was diagnosed with residual stomach cancer and underwent total gastrectomy and distal pancreatectomy. Three months after the surgery, a local recurrence and the involvement of para-aortic lymph node were diagnosed using computed tomography. The chemotherapy treatment(S-1, cisplatin, trastuzumab)was prescribed. However, the disease has progressed. Paclitaxel and ramucirumab were given for second-line, nivolumab for third-line and irinotecan for fourth-line. During that, tumor at local recurrent site invaded to the portal vein. The patients received 50 Gy in 25 fractions of radiotherapy. A remarkable reduction of the mass was shown. In addition to this, we observed that spontaneous shrinking of the para-aortic lymph node metastasis, which was located out of the radiation field. We observed a rare radiation-induced abscopal effect. Radiotherapy might represent a potential candidate for a combination with immunotherapy. A combination of immunotherapy as well as chemotherapy with radiotherapy represents a promising therapeutic strategy.

177Lu-PSMA-617 RLT in mCRPC: A single center experience, the earlier could be the better.

INTRODUCTION: Radioligand therapy which targets the prostate specific membrane antigen (PSMA) has recently considered as option in the treatment of metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to evaluate the biochemical, clinical and radiological data of patients received treatment with 177Lu-PSMA-617 RLT in our clinic following the diagnosis of mCRPC, and to investigate the relationship between treatment timing and metastasis region and survival. MATERIAL AND METHODS: This is a retrospective, observational, single-center study from December 2016 to December 2019. Patients underwent 177Lu-PSMA-617 RLT with a diagnosis of mCRPC. We used the Kaplan-Meier test and the Cox regression proportional hazard test to assess survival data. RESULTS: 95 patients with an average age of 70.45 (50-85) were evaluated retrospectively. Median follow-up was 10.86 months (8.15-11.94 months) and the median lines of 177Lu-PSMA-617 RLT treatment was 4 (1-5). Median overall survival was found to be 17.03 ±â€¯5,78 months in the patients receiving the treatment at the third or lower lines while it was 10,30 ±â€¯0,93 months in patients receiving the treatment at the fourth or higher lines (p = 0.021). When evaluating patients with only bone metastasis and patients with bone and lymph node metastasis, the median overall survival was 11.46 ±â€¯0.87 months and 12.13 ±â€¯3.02 months (p = 0.445), respectively. CONCLUSION: 177Lu-PSMA-617 RLT treatment provides better survival in the treatment of patients diagnosed with mCRPC after standard treatments and received it earlier. 177Lu-PSMA-617 RLT treatment could be an effective treatment method in mCRPC patients with bone and lymph node metastasis.

IMNI PRECISION trial protocol: a phase II, open-label, non-inferior randomized controlled trial of tailoring omission of internal mammary node irradiation for early-stage breast cancer.

BACKGROUND: Since the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined. METHODS: The IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically "high risk" BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score "low risk" (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival. DISCUSSION: The IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04517266 . Date of registration: August 18, 2020. Status: Recruiting.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography-based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline.

BACKGROUND: Approximately 20-40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). OBJECTIVE: To evaluate and validate the updated NRG 2020 guideline with our established LN atlas. DESIGN, SETTING, AND PARTICIPANTS: We screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10-90%), or outside (<10%). RESULTS AND LIMITATIONS: In comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. CONCLUSIONS: The updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. PATIENT SUMMARY: We compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Postoperative radiation therapy improves prognoses in extramammary Paget's disease presenting with multiple lymph node metastases.

Invasive extramammary Paget's disease may cause lymph node and distant metastases. Complete lymph node dissection is generally performed for extramammary Paget's disease presenting with lymph node metastases. Patients with extramammary Paget's disease and multiple lymph node metastases typically have poor prognoses, and there is no effective postoperative treatment to prevent recurrence or further metastases in such patients to date. This study aimed to evaluate the efficacy of postoperative radiotherapy in patients with extramammary Paget's disease and multiple lymph node metastases. We enrolled 26 patients with extramammary Paget's disease with ≥3 lymph node metastases who were treated at the National Cancer Center Hospital in Japan between January 2000 and June 2021. The patients were divided into those who underwent complete lymph node dissection only or with postoperative radiotherapy. We evaluated recurrence-free survival, distant metastasis-free survival, and overall survival outcomes with Kaplan-Meier curves. Among the 26 enrolled patients, 16 underwent complete lymph node dissection only and 10 underwent complete lymph node dissection with postoperative radiotherapy. The median follow-up period was 16 months. The 5-year recurrence-free, distant metastasis-free, and overall survival values were 47.3%, 63.0%, and 90% in those with complete lymph node dissection and postoperative radiotherapy, while these outcomes were all 0% (p = 0.001, 0.004, and 0.009, respectively) in those with only complete lymph node dissection. Thus, survival was significantly prolonged with postoperative radiotherapy. Additional postoperative radiotherapy may substantially improve the prognoses of patients with extramammary Paget's disease and ≥3 lymph node metastases, and undergoing curative surgery.

Level Ib CTV delineation in nasopharyngeal carcinoma based on lymph node distribution and topographic anatomy.

BACKGROUND AND PURPOSE: To analyze the distribution pattern of lymph nodes (LNs) metastasis of level Ib in nasopharyngeal cancer (NPC) and propose shrinkage of clinical target volume (CTV) boundaries to avoid unnecessary radiation for some space with very low-risk of involvement. MATERIALS AND METHODS: Pretreatment images of pathologically proven NPC patients were reviewed and those with positive level Ib LN metastasis was enrolled. The geometric center of each level Ib LN in the neck was marked on a template CT. The spatial relationship of nodes with key structures in level Ib was analyzed. Modified level Ib CTV according to the 2013 International CTV consensus was proposed based on the LN distribution pattern. A PlanIQ Feasibility DVH module was implemented to evaluate the feasibility analysis of the best possible sparing of organs at risk (OAR) with modified Ib CTV. RESULTS: A total of 1518 NPC patients were reviewed and 54 with positive level Ib nodes were enrolled. Four sub-level anatomical regions were defined within the gross area of level Ib. Of 106 positive nodes identified, none, one, 88, and 17 were found in the intraglandular (IG), medial mandibular (MM), supra perivascular (SP), and infra perivascular (IP) sub-level, respectively. This study proposes sparing the IG and MM sub-level and including the area within a specified distance from the submandibular gland (11 mm for SP, 17 mm for IP) for CTV coverage. Compared with planning based on CTV-consensus, planning based on CTV-proposed results in a significantly reduced CTV volume, and mean dose (Dmean) of both the ipsilateral SMG and bilateral SLG. CONCLUSIONS: Based on detailed analysis of the relationship between positive node distribution and several important anatomical structures, modified level Ib CTV for prophylactic irradiation was proposed to reduce the dose of OAR irradiation.

Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial.

PURPOSE: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. METHODS: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. RESULTS: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5­year disease-free survival (DFS) was 95.0% (85.9-100%) in group 1 and 93.0% (86.3-100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100-100%) in group 1 and 97.4% (92.4-100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2-99.4%) and 96.9% (91.5-100.0%), respectively. For groups 1 and 2, the 5­year outcomes were 5.0% (0.0-14.4%) and 2.3% (0.0-6.1%) for local recurrence (p = 0.51), and 6.2% (0.0-17.4%) and 7.0% (0.0-13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0-14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0-0.0%). CONCLUSION: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.