International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy.

BACKGROUND: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT). METHODS: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). RESULTS: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. CONCLUSIONS: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

Treatment of cerebral radiation necrosis with nerve growth factor: A prospective, randomized, controlled phase II study.

PURPOSE: A prospective, placebo controlled phase II trial was conducted to test the efficacy of Nerve Growth Factor (NGF) for the treatment of symptomatic temporal lobe necrosis (TLN). MATERIALS AND METHODS: Patients with progressive TLN were randomly assigned to either the control or the study group in a 1:1 ratio. The control group received corticosteroids with gradually reduced dosage. The study group received NGF with corticosteroids. NGF was dissolved in 2mL normal saline and injected intramuscularly at 18µg/time, once a day for 2months. The efficacy was evaluated by both the objective and subjective methods every 3-4months after treatment. The objective method compared volumes of the necrotic masses on MRI before and after treatment. The subjective method compared the neurocognitive score as evaluated by the mini-mental status examination (MMSE). RESULTS: Twenty-eight cases were enrolled into this study. The objective evaluation showed that the response rate (RR) in the study group was higher than the control group. The ratio was 10 versus 2 (p=0.006), and 12 versus 3 (p=0.002) at 3-4months and 6-8months after intervention, respectively. The subjective evaluation demonstrated both groups were effective in controlling the necrosis related symptoms in the first 6months after treatment. But NGF was more effective than corticosteroids at 9months (13 versus 4, p=0.001). The only observed side effect was mild pain at the injection site in 3 patients in the study group. CONCLUSIONS: Our results demonstrated that the process of TLN is not irreversible. NGF is more effective in recovering TLN than corticosteroids with little side effect. NGF has a longer duration in controlling the necrosis related symptoms than corticosteroids.

Dosimetric evaluation of 4 different treatment modalities for curative-intent stereotactic body radiation therapy for isolated thoracic spinal metastases.

To investigate the dosimetric characteristics of 4 SBRT-capable dose delivery systems, CyberKnife (CK), Helical TomoTherapy (HT), Volumetric Modulated Arc Therapy (VMAT) by Varian RapidArc (RA), and segmental step-and-shoot intensity-modulated radiation therapy (IMRT) by Elekta, on isolated thoracic spinal lesions. CK, HT, RA, and IMRT planning were performed simultaneously for 10 randomly selected patients with 6 body types and 6 body + pedicle types with isolated thoracic lesions. The prescription was set with curative intent and dose of either 33Gy in 3 fractions (3F) or 40Gy in 5F to cover at least 90% of the planning target volume (PTV), correspondingly. Different dosimetric indices, beam-on time, and monitor units (MUs) were evaluated to compare the advantages/disadvantages of each delivery modality. In ensuring the dose-volume constraints for cord and esophagus of the premise, CK, HT, and RA all achieved a sharp conformity index (CI) and a small penumbra volume compared to IMRT. RA achieved a CI comparable to those from CK, HT, and IMRT. CK had a heterogeneous dose distribution in the target as its radiosurgical nature with less dose uniformity inside the target. CK had the longest beam-on time and the largest MUs, followed by HT and RA. IMRT presented the shortest beam-on time and the least MUs delivery. For the body-type lesions, CK, HT, and RA satisfied the target coverage criterion in 6 cases, but the criterion was satisfied in only 3 (50%) cases with the IMRT technique. For the body + pedicle-type lesions, HT satisfied the criterion of the target coverage of ≥90% in 4 of the 6 cases, and reached a target coverage of 89.0% in another case. However, the criterion of the target coverage of ≥90% was reached in 2 cases by CK and RA, and only in 1 case by IMRT. For curative-intent SBRT of isolated thoracic spinal lesions, RA is the first choice for the body-type lesions owing to its delivery efficiency (time); the second choice is CK or HT; HT is the preferential choice for the body + pedicle-type lesions. This study suggests further clinical investigations with longer follow-up for these studied cases.

Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study.

BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.

Study of the medial group retropharyngeal node metastasis from nasopharyngeal carcinoma based on 3100 newly diagnosed cases.

PURPOSE: Patterns of metastases to the medial retropharyngeal lymph nodes (RPLN) from nasopharyngeal carcinoma (NPC) have gain little attention. Since the incidence of dysphagia was closely related to whether the medial RPLN was irradiated, we carried out a prospective study to explore the patterns of the medial RPLN involvement. METHODS AND MATERIALS: Previously untreated NPC patients were required to receive MRI scan. MRI scanning sequences included pre-contrast T1WI, T2WI, and post-contrast T1WI with fat suppression. All images were evaluated by the multi-disciplinary treatment group of NPC. RESULTS: 3100 cases of NPC entered this study. 2679 (86.4%) cases had involved lymph nodes. The detailed distribution were: 2341 (87.4%) in level IIb, 1798 (67.1%) in level IIa, 1184 (44.2%) in level III, 350 (14.1%) in level IV, 995 (37.1%) in level V, 115(4.3%) in level Ib, 2012 (75.1%) in the retropharyngeal area. But only 6 (0.2%) were located at the medial group, accompanied with the lateral RPLN and other node metastasis. Only one medial RPLN can be identified in a patient, whereas the number of the lateral RPLNs per affected side varied between one and four. The average size of the medial and lateral RPLNs was 8±4 mm (range, 4-17 mm) and 16±9 mm (range, 5-53 mm), respectively. CONCLUSIONS: ① Involvement of the retropharyngeal nodes were mainly located at the lateral group, the medial RPLN was rarely seen. ② Metastasis to the medial RPLN was always accompanied with other node metastasis. ③ Only one medial RPLN can be identified in a patient, whereas the enlarged lateral RPLNs per affected side could be multiple. ④ The average size of the medial RPLN was smaller than the lateral RPLNs.

The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma.

BACKGROUND: The authors prospectively evaluated the correlation between technetium-99m methoxyisobutyl isonitrile ((99m) Tc-MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: Eighty-six patients with locally advanced NPC underwent single-photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) (99m) Tc-MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between (99m) Tc-MIBI accumulation in tumors and response to chemotherapy with 5-FU/DDP was examined. RESULTS: Positive accumulation of (99m) Tc-MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5-FU/DDP chemotherapy in patients who had positive (99m) Tc-MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative (99m) Tc-MIBI accumulation (TUR ≤ 1.1; 98.7% vs 10%; P < .001). CONCLUSIONS: Patients with negative (99m) Tc-MIBI accumulation were resistant to 5-FU/DDP chemotherapy. (99m) Tc-MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5-FU/DDP and can help in the selection of patients for induction chemotherapy.

Patterns of retropharyngeal node metastasis in nasopharyngeal carcinoma.

PURPOSE: To explore the pattern of metastasis to retropharyngeal lymph nodes (RLN) and its relationship with tumor range in nasopharyngeal carcinoma (NPC) patients by using magnetic resonance imaging. METHODS AND MATERIALS: Magnetic resonance images of 618 NPC patients were reviewed. Nodes were classified as metastatic on the basis of size criteria, the presence of nodal necrosis, and extracapsular spread. RESULTS: A total of 597 involved RLN were detected in 392 patients (63.4%). The sites of RLN metastasis included occipital bone, 37 (6.2%); first cervical vertebra (C1), 453 (75.9%); second cervical vertebra (C2), 104 (17.4%); and third cervical vertebra (C3), 3 (0.5%). The incidence of RLN involvement was less than that of Level IIb node involvement (72.2% vs. 86.5%) in 543 patients with lymphadenopathy. The incidence of RLN metastasis was significantly higher in cases of parapharyngeal space invasion or involvement of Level II, Level III, Level IV, and/or Level V nodes and significantly lower in N0 and Stage I disease. Conversely, the incidence of RLN metastasis did not differ significantly among T1, 2, 3, and 4 disease or among Stage II, III, and IV disease. CONCLUSIONS: Level IIb nodes, rather than RLN, seem to be the first-echelon nodes in NPC. The incidence of RLN metastasis decreases steadily from level C1 to level C3. Retropharyngeal lymph node metastasis correlates well with involvement of the parapharyngeal space and metastases to Level II, III, IV, and/or V nodes but not with T stage.

[Analysis of computed tomography-based distribution of metastatic cervical nodes in 218 cases of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: The application of intensity- modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) requires a precise delineation of the nodal area and nodal clinical target volume (CTV) on computed tomography (CT) images,and the prerequisite is to find out the rules of CT-based distribution of metastatic lymph nodes of NPC. This study was designed to analyze the rules of CT-based distribution of nodal involvements of NPC according to the guidelines of nodal levels proposed by Radiation Therapy Oncology Group (RTOG). METHODS: From Jul. 2003 to Nov.2003, 259 newly diagnosed NPC patients received radiotherapy at Fudan University Affiliated Cancer Hospital. All patients had transversal contrast enhanced CT scan from base of skull to clavicle before treatment. Diagnostic radiologists and radiation oncologists together assessed the nodal distribution in each RTOG nodal level. Chi-square test was used to analyze the correlation between T stage and nodal metastasis rate. The neck was further divided into 3 regions by the verge of hyoid bone and the inferior border of cricoid cartilage to assess leap metastasis of nodes. RESULTS: A total of 218 patients (84.2%)had nodal involvement. The distribution was as follow: 0 in level Ia, 6 (2.8%) in level Ib, 115 (52.8%) in level IIa,192 (88.1%) in level IIb, 78 (35.8%) in level III, 20 (9.2%) in level IV, 65 (29.9%) in level V, 0 in level VI,157 (72.0%)in retropharynx, and 2 (0.9%) at preauricular area. Leap metastases were found in only 5 patients (2.3%). No significant correlation was found between T stage and nodal involvement. CONCLUSION: NPC has a high probability of nodal metastases, nodes in level IIa,IIb, and retropharynx are most likely to be involved. Nodes metastasized mostly from the upper to the lower level, and from the proximal to the distal part, with a very low leap metastasis rate. The relationship between T stage and nodal involvement has no statistical significance.