Chemoradiotherapy Group Research Articles

MANAGING LOCALLY ADVANCED CERVICAL CARCINOMA WITH A PELVIC KIDNEY USING VOLUMETRIC MODULATED ARC THERAPY: A CLINICAL CHALLENGE

The coexistence of cervical carcinoma and pelvic kidney is uncommon. Given that the pelvic kidney occupies the traditional radiation field for cervical carcinoma, treating these patients with radiation poses a therapeutic dilemma. We report the case of a 72 years old patient with stage IIIB cervical carcinoma with an incidental diagnosis of pelvic kidney was treated with radical chemoradiotherapy using volumetric-modulated arctherapy with concurrent weekly cisplatin.. At the 12-month follow-up, the patient was disease free and had no deterioration in kidney function. Volumetric-modulated arc therapy (VMAT) allowed for the precise delivery of high radiation doses in this particular case, while effectively sparing the kidney.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Survival outcome of esophagectomy and chemoradiotherapy for resectable esophageal squamous cell carcinoma in patients >75 years of age.

The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

Novel pretreatment nomograms based on pan-immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma.

The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.

Long term results of a randomized phase III study of nimotuzumab in combination with concurrent radiotherapy and cisplatin versus radiotherapy and cisplatin alone, in locally advanced squamous cell carcinoma of the head and neck.

LBA6092 Background: The addition of nimotuzumab to weekly cisplatin as a radiosensitizer had improved progression-free survival (PFS) in a phase 3 study in locally advanced head and neck squamous cell carcinoma (LA HNSCC). However, whether it leads to an improvement in long-term OS is unknown. Hence this analysis was performed to evaluate the efficacy (in terms of OS) and late-term adverse events of the addition of nimotuzumab to concurrent chemoradiation in LA HNSCC. Methods: This was an open-label, investigator-initiated, phase 3 randomized trial conducted from 2012 - 2018. 536 adult patients with LA HNSCC, fit for radical chemoradiation were randomly assigned. Primary sites in the nasopharynx, salivary gland, nasal cavity, and paranasal sinus were excluded. Randomized 1:1 to either radical radiotherapy (66-70 Gy) with concurrent weekly cisplatin (30 mg/m2) (CRT) or the same schedule of chemoradiation with weekly nimotuzumab (200 mg) (NCRT). The primary endpoint was a 10-year OS; the key secondary endpoint was late adverse events. Intent to treat analysis was performed. OS was defined as the time from randomization till death. Kaplan Meier method will be used for the estimation of OS. Landmark analysis was performed to compare 10 OS between the 2 arms. COX proportional hazard model will be used for the calculation of hazard ratio (HR). The adverse events between the 2 arms were compared using a Fisher's test. A p-value of 0.05 will be considered as significant. Results: The median follow-up was 8.86 years (95% CI 8.59-9.16). The primary site of the primary was the oropharynx (269,50.2%) and only 24 cases were HPV positive. The 10-year OS was 22.5% (95% CI 16.7-28.8) versus 33.5% (95% CI 27.6-39.4) in the CRT and NCRT arm respectively (Hazard ratio=0.811; 95%CI 0.664-0.995, P=0.044). The median OS was 2.78 years (95% CI 2.31-3.69) versus 3.69 years (95% CI 2.90-4.49) in the CRT and NCRT arm respectively (P value by log-rank test=0.04). The median OS in HPV negative oropharynx was 1.8 years (95% CI 1.51-2.09) versus 2.48 years (95% CI 1.79-3.16) in the CRT and NCRT arm respectively (P value by log-rank test=0.02; HR 0.724 95%CI 0.546-0.959). Long-term adverse events were captured in 380 patients. There was no statistically significant difference in late-term adverse events between the 2 arms and will be presented at the conference. Conclusions: The addition of nimotuzumab to weekly cisplatin leads to improvement in long-term overall survival in locally advanced HNSCC without any additional increase in late-term adverse events. These results are largely applicable in HPV-negative patients. Clinical trial information: CTRI/2014/09/004980 .

Nivolumab combined with radical chemoradiotherapy sparing concurrent cisplatin in high-risk locoregionally advanced nasopharyngeal carcinoma (PLATINUM): An investigator-initiated, open-label, multicenter, single-arm, phase II clinical trial.

6080 Background: The current standard therapy for locoregionally advanced nasopharyngeal carcinoma (LANPC) is radical chemoradiotherapy using induction chemotherapy plus concurrent chemoradiotherapy. However, concurrent cisplatin leads to severe acute (54.0–61.0%) and late (9.2–11.4%) toxicities. We hypothesized that nivolumab combined with radical chemoradiotherapy sparing concurrent cisplatin would obtain promising survival and low toxicity in high-risk LANPC. Methods: In this single-arm, phase II clinical trial (NCT03984357), patients with high-risk LANPC (T4N1M0 or T1–4N2–3M0) were recruited from 7 hospitals in China to receive nivolumab (360 mg once every 3 weeks for 3 cycles [Q3W x 3]) + induction chemotherapy (gemcitabine 1000 mg/m2 + cisplatin 80 mg/m2, Q3W x 3), followed by nivolumab (360 mg, Q3W x 3) + intensity-modulated radiotherapy (PGTVnx, 70Gy/33fx), and thereafter adjuvant nivolumab (480 mg, Q4W x 6). The primary end point was 3-year failure-free survival (FFS), defined as the time from enrollment to any disease failure or death. Secondary end points were safety and quality-of-life (QoL) assessed by cellphone-based EORTC/FACT questionnaires. Results: Between April 2020 and October 2020, 152 patients (median [IQR] age, 49 [39–56] years; 18.4% women) were included. After a median follow-up of 39 months (≥ 36 months, 89.5%), the 3-yr FFS was 88.8% (95% CI, 83.9–94.0%) and the 3-yr overall survival was 98.0%. Sixty (40.2%) patients had grade 3–4 acute treatment-related adverse events (trAEs) throughout treatment; 11 (7.2%) were associated with potential immunologic causes mainly involving hepatic (aspartate aminotransferase increased, 3.3%) and skin toxicities (rash/dermatitis, 2.0%). A total of 123 patients completed all required treatment, including 6 cycles of adjuvant nivolumab, with an overall compliance rate of 80.9%. The incidences of grade 3–4 acute trAEs in the induction, radiotherapy, and adjuvant phases were 30.2%, 16.7%, and 6.0%, respectively; compliance rates, 95.4%, 96.5%, and 91.8%, respectively. Eight (5.2%) patients had grade 3–4 late trAEs, e.g., hearing impaired (3.3%) and dry mouth (0.7%). No treatment-related death was observed. Patients had consistent negative changes in general QoL from baseline between the radiotherapy and induction phases, except for the domains of global health status and physical function/well-being, which were more common during the radiotherapy phase. Conclusions: Nivolumab incorporated into induction chemotherapy followed by radiotherapy has a promising efficacy and low toxicity for high-risk LANPC patients. A phase 3 non-inferior randomized clinical trial assessing PD-1 blockade plus this de-intensified radical chemoradiotherapy is underway (NCT04907370). Clinical trial information: NCT03984357 .

Conversion surgery for tislelizumab combined chemotherapy for T4a/N3 esophageal squamous cell carcinoma (ESCC): A prospective, single-arm, phase II study.

4069 Background: T4a/N3 ESCC is treated with neoadjuvant concurrent chemoradiotherapy plus surgery or radical chemoradiotherapy according to NCCN guidelines. This study aimed to evaluate the safety and efficacy of conversion therapy of Tislelizumab combined with chemotherapy in patients with T4a/N3 ESCC. Methods: This is a prospective, single-arm, single-center clinical trial. A total of 40 patients with newly diagnosed ESCC (cT4a/N3) received 2-4 cycles of paclitaxel (135 mg/m2) on day 1, and cisplatin (80 mg/m2) on day 1, Tislelizumab (200 mg) on day 2, every 3 weeks. After an efficacy evaluation, the patients will undergo radical esophagectomy resection within 4-6 weeks after conversion therapy. The primary endpoints are the safety and the R0 resection rate. The secondary endpoints include the objective response rate (ORR), a postoperative pathological complete response (pCR), major pathological response (MPR), overall survival (OS), disease-free survival (DFS). Exploratory endpoint is to examine immune biomarker of the efficacy of conversion therapy for ESCC. Results: 40 patients were enrolled, the ORR was 95%(38/40), and 60% (24/40) patients who completed conversion treatment underwent esophagectomy. R0 resection rate was 100% (24/24) with no reoperations or perioperative deaths. 70% (28/40) patients experienced at least one treatment-related adverse event (TRAE) and 12.5% (5/40) patients reported grade 3 and above TRAEs. For these surgical patients, the MPR and pCR rates were 33% (8/24) and 20.8% (5/24) respectively. Flow cytometry showed that the percentage of CD3+CD4+CD8-T cells was significantly increased in peripheral blood after conversion therapy (p-value 0.02). Conclusions: Tislelizumab combined with chemotherapy, followed by radical esophagectomy resection has promising efficacy and good safety for T4a/N3 ESCC. Clinical trial information: NCT05449483 .

Endoscopic surgery combined chemoradiotherapy and PD-1 blockade in patients with sinonasal mucosal melanoma.

e21552 Background: Primary sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease different from cutaneous melanoma. The best treatment modality including the role of immune checkpoint blockade in SNMM has not been defined. Methods: Between 2021 and 2023, patients with previously untreated sinonasal melanoma were enrolled by three single-center investigator-initiated phase II clinical trials (ChiCTR2100046498 / ChiCTR2100045797/ ChiCTR2100049031). Eligible patients in ChiCTR2100045797 trial received postoperative radical chemoradiotherapy combined with toripalimab (a PD-1 inhibitor) for a year or until the disease progressed. Eligible participants in ChiCTR2100046498 study received surgery combined with radiation without immunotherapy. And for patients in ChiCTR2100049031 study, preoperative radiation was carried out firstly. The locoregional control, distant metastasis-free survival (DMFS), and overall survival (OS) were the main efficacy goals. Results: Fifty-four patients were enrolled (mean age 62 years, 33 males [61.1%] and 21 women [38.9%]) with 2y-OS rate 62.3±7.9%, 2y-RFS rate 67.1±8.2%, and 2y-DMFS rate 63.9±8.1%. Patients with T3 (n = 23), T4a (n = 14), and T4b (n = 17) stages, including12 patients with node-positive disease, were included at baseline. During a median follow-up of 11 months, 19 patients ultimately died, 10 experienced relapses, and 17 developed metastases. Tumor T staging was demonstrated to be an independent prognostic predictor according to the Cox univariate analysis. The primary factor contributing to a poor prognosis and the primary cause of death for 73.7% of patients was distant metastases. Preoperative radiation had an improved long-term survival with 2y-OS rate of 85.7±13.2%, and it can considerably lower the risk of distant metastases (p≤0.05). The overall survival rate for patients receiving postoperative chemoradiotherapy combined with immunotherapy was higher than that for patients not receiving immunotherapy (2y-OS rate 74.1±11.4% vs. 39.3±15.8%), although the difference was not statistically significant due to a small number of patients (p = 0.16). No immune-related adverse effects grade≥3 was recorded. Conclusions: The primary cause of the poor prognostic performance of SNMM is distant metastasis. The risk of distant metastases might be considerably decreased by preoperative radiation treatment. Surgery combined with radiation and immunotherapy could bring promising survival benefit. The way forward may involve investigating the combination of immunotherapy and preoperative radiotherapy. Clinical trial information: NCT04879654 ; NCT05009446 .

233P 3-year outcome of radical chemoradiotherapy for anal squamous cell carcinoma (ASCC) using intensity-modulated radiation therapy (IMRT) protocol at Southend Hospital

233P 3-year outcome of radical chemoradiotherapy for anal squamous cell carcinoma (ASCC) using intensity-modulated radiation therapy (IMRT) protocol at Southend Hospital

The reality of recovery – auditing weight changes in human papilloma positive oropharyngeal (HPV+OPX) patients who have completed radical chemoradiation (CRT)

The reality of recovery – auditing weight changes in human papilloma positive oropharyngeal (HPV+OPX) patients who have completed radical chemoradiation (CRT)

Acute hematologic toxicity prediction using dosimetric and radiomics features in patients with cervical cancer: does the treatment regimen matter?

Acute hematologic toxicity (HT) is a prevalent adverse tissue reaction observed in cervical cancer patients undergoing chemoradiotherapy (CRT), which may lead to various negative effects such as compromised therapeutic efficacy and prolonged treatment duration. Accurate prediction of HT occurrence prior to CRT remains challenging. A discovery dataset comprising 478 continuous cervical cancer patients (140 HT patients) and a validation dataset consisting of 205 patients (52 HT patients) were retrospectively enrolled. Both datasets were categorized into the CRT group and radiotherapy (RT)-alone group based on the treatment regimen, i.e., whether chemotherapy was administered within the focused RT duration. Radiomics features were derived by contouring three regions of interest (ROIs)-bone marrow (BM), femoral head (FH), and clinical target volume (CTV)-on the treatment planning CT images before RT. A comprehensive model combining the radiomics features as well as the demographic, clinical, and dosimetric features was constructed to classify patients exhibiting acute HT symptoms in the CRT group, RT group, and combination group. Furthermore, the time-to-event analysis of the discriminative ROI was performed on all patients with acute HT to understand the HT temporal progression. Among three ROIs, BM exhibited the best performance in classifying acute HT, which was verified across all patient groups in both discovery and validation datasets. Among different patient groups in the discovery dataset, acute HT was more precisely predicted in the CRT group [area under the curve (AUC) = 0.779, 95% CI: 0.657-0.874] than that in the RT-alone (AUC = 0.686, 95% CI: 0.529-0.817) or combination group (AUC = 0.748, 95% CI: 0.655-0.827). The predictive results in the validation dataset similarly coincided with those in the discovery dataset: CRT group (AUC = 0.802, 95% CI: 0.669-0.914), RT-alone group (AUC = 0.737, 95% CI: 0.612-0.862), and combination group (AUC = 0.793, 95% CI: 0.713-0.874). In addition, distinct feature sets were adopted for different patient groups. Moreover, the predicted HT risk of BM was also indicative of the HT temporal progression. HT prediction in cervical patients is dependent on both the treatment regimen and ROI selection, and BM is closely related to the occurrence and progression of HT, especially for CRT patients.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer

BackgroundEvaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC).MethodsRetrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs).ResultsA total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314–0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343–0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05).ConclusionsIn LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Dosimetric Analysis of Computed Tomography-Based Brachytherapy Planning in Carcinoma Cervix

Background The standard of care for locally advanced cervical cancer is concurrent chemoradiation followed by intracavitary brachytherapy (BT). BT forms an integral part of management as it improves local control and overall survival. In recent times, image-guided BT (IGBT) has been recommended as the standard of care. Computed tomography (CT) scan-based BT is a cost-effective and easily available modality for IGBT. The aim of the study was to do a dosimetric analysis of CT scan-based BT for patients with cervical cancer. Methods This was a retrospective study and included patients with cervical cancer treated with radical chemoradiation followed by BT. CT scan was done before every fraction after applicator placement, and CT-based planning was done for all fractions. Clinical details were abstracted from the case records, and dosimetric details were collected from the treatment planning systems. Total equivalent dose in 2 Gy per fraction (EQD2) was calculated for external beam radiation therapy and BT target volumes and organs at risk (OARs). Results This study included 50 patients. The mean age was 45 years. The majority of the cases were stage III. The mean high-risk clinical target volume (HRCTV) for the 1st, 2nd, and 3rd fraction was 53.1, 52.1, and 51.3 mL, respectively. Mean D90 HRCTV (dose received by 90% of the HRCTV) dose was 81.4 Gy (EQD2 10 Gy) and D2cc was 75.8 Gy (EQD2 3 Gy) for the rectum and sigmoid and 86.2 Gy (EQD2 3 Gy) for the bladder. Conclusion CT-based BT is a reasonable option in high-volume and low-resource settings where the availability of magnetic resonance imaging is limited. CT-based BT at every fraction can ensure proper applicator placement and aid in optimizing the dose to the target volumes and OARs.

The quality of life outcome in patients with head and neck squamous cell cancer treated using chemoradiotherapy

ObjectiveOrgan preservation is a goal of head and neck squamous cell cancer (HNSCC) treatment. chemoradiotherapy remains one of the main treatment options and is widely recognized as a method with organ-preserving potential and outcomes comparable to those of surgery. However, few studies have investigated the quality of life (QOL) of patients with HNSCC treated using chemoradiotherapy, therefore, we aimed to retrospectively evaluate how QOL changes pre and post-chemoradiotherapy. MethodsWe evaluated QOL outcomes in patients who underwent initial radical chemoradiotherapy for HNSCC at the Department of Otolaryngology and Head and Neck Surgery Kitasato University Hospital from 2018 to 2021. We used the Cancer Fatigue Scale (CFS) and the combined European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 questionnaires at pre-treatment, three months and six months post-treatment. ResultsWe obtained 37 and 29 responses from the CFS and EORTC QLQ-C30/H&N35 questionnaire, respectively. From the CFS, the physical fatigue score at three months post-treatment deteriorated more than that at pre-treatment, and significantly improved by six months post-treatment. The total score worsened significantly at three months and there was a trend toward improvement at six months. In the EORTC QLQ-C30, physical and social functioning declined in three months and did not improve within six months. Fatigue was substantially worse at three months and significantly improved at six months but did not reach the same level as that before treatment. Appetite loss was also significantly worse at three months. In the QLQ-H&N35 questionnaire, sensory issues, trouble with social contact, and dry mouth were significantly worse at three months and did not improve within six months. Sticky saliva also worsened at three months and significantly improved at six months. ConclusionThere were some problems associated with chemoradiotherapy. Some patients showed an improvement, while others continued to have challenges. In Japan, chemoradiotherapy was shown to have a long-term impact on the patient's life.

369: Outcomes following complete response on MRI following radical chemoradiotherapy for cervical cancer

369: Outcomes following complete response on MRI following radical chemoradiotherapy for cervical cancer

Narrow band imaging-based radiogenomics for predicting radiosensitivity in nasopharyngeal carcinoma

ObjectivesThis study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. MaterialsThe study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. ResultsAfter feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. ConclusionNBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.

Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study.

This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients. Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns. The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching. Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.

Anti-angiogenesis agents plus chemoradiotherapy for locally advanced nasopharyngeal cancer: a systematic review and meta-analysis.

To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies). A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05-1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12-1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16-11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04-3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05). Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma. https://inplasy.com/inplasy-2023-8-0076/ , registration number INPLASY202380076.