Local Disease Control Research Articles

Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for unresectable locally advanced pancreatic cancer (TIGeR-PaC): A randomized phase 3 multicenter study.

TPS773 Background: Prognosis for locally advanced pancreatic cancer (LAPC) remains dismal even with advances in cancer therapy. Beyond systemic therapies, local disease control is important in these patients. Local double balloon mediated delivery of intra-arterial gemcitabine (IAG) was demonstrated to be safe in this patient population in a prior study1. TIGeR-PaC is an ongoing Phase-3 clinical trial comparing the efficacy of this approach compared to standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC. Methods: The trial is designed with an induction phase of upfront systemic therapy prior to IAG. Patients with LAPC diagnosed within 6 weeks and ECOG 0-1, receive 3 cycles of GN and 1 cycle of radiation. The form of radiation was either IMRT, 50 Gy in 25 fractions, with concomitant capecitabine or SBRT, 33 Gy in 5 fractions (per site preference). Following induction, patients with non-progressive disease were randomized to receive IAG (8 treatments every two weeks for 16 weeks) or continuing therapy with 4 cycles of GN. After the 16 weeks of randomized therapy, the patients with non-progressive disease went on to continue systemic therapy (GN or capecitabine, per investigator’s preference) until disease progression and then followed for survival only. The primary endpoint is overall survival, and the study has an 80% power to detect a hazard ratio of 0.6 between the two arms. As of September 1st, 2022, 189 patients have been enrolled in the trial. In its initial design the trial expected a 35% drop out rate during the induction phase; however, two years into the trial the actual observed dropout rate was 53%. Beyond progression (22%), the key element of dropout rate was AE/SAE during radiation with IMRT/capecitabine (17%) vs. only 6% with SBRT. To increase accrual of randomized patients, the protocol and the statistical plan were modified to restrict the mode of radiation during induction to SBRT only starting December 2021. Since the modification of the protocol, the dropout rate during induction has decreased to 38%. As of this abstract, 43 patients have been randomized following induction with GN and SBRT. The rate of SAE during active treatment is not different between the 2 arms (20% in each arm), and the most common SAE is GI side effects in both arms. The protocol has a pre-planned interim analysis after 26 events, with 23 events at this writing we expect our first interim analysis later this year. 1. Rosemurgy AS, e al: J Pancreat Cancer. 2017;3(1):58-65. doi:10.1089/pancan.2017.0011. Clinical trial information: NCT03257033 .

Axial Axis Metastasis.

Axial axis metastasis remains a challenge for surgical as well as other treatment modalities, like chemotherapy, immunotherapy, and radiotherapy. It is unequivocal that surgery provides pain improvements and preservation of neurological status, but this condition remains when associated with radiotherapy and other treatment modalities. In this review, we emphasize the current forms of surgical treatment in the different regions of the spine and pelvis. The evident possibility of percutaneous treatments is related to early or late cases, and in cases in which there are greater risks and instability to conventional surgeries associated with radiotherapy and have been shown to be the appropriate option for local control of metastatic disease.

Toxicity and efficacy of stereotactic body radiation therapy vs. intensity-modulated radiation therapy for the treatment of locally advanced pancreatic cancer in a phase 3 trial.

713 Background: Locally advanced pancreatic cancer (LAPC) remains one of the deadliest cancers. Radiation is listed as a first line therapy option in treatment guidelines and remains a common treatment for this patient population primarily for local disease control and symptoms. Herein, we performed an exploratory analysis to compare the toxicity and efficacy between patients receiving either stereotactic body radiation therapy (SBRT) or intensity-modulated radiation therapy (IMRT) during the induction phase (prior to randomization) of a Phase 3 trial for localized intra-arterial gemcitabine therapy. Methods: As part of the TIGeR-PaC Phase 3 trial, patients with LAPC and an ECOG of 0-1 underwent an induction phase and were treated with 2 cycles of gemcitabine and nab-paclitaxel prior to receiving SBRT (n=59; 33Gy in 5 Fractions) or IMRT (n=75; 50Gy in 25 fractions) with concurrent PO capecitabine BID Monday-Friday. We performed Mann-Whitney analyses to compare mean percent changes in tumor size (imaging performed prior and 1-month after radiation) and CA 19-9 tumor markers. Adverse event (AE) incidence data during and 2 weeks after completion of the last fraction of radiation was used to compare toxicity via a contingency table. Results: A total of 134 patients across 22 sites (63 male/71 female; median age: 68.5 years) underwent radiation with no significant difference in baseline demographics between SBRT and IMRT patients. The decision for SBRT vs. IMRT was site-driven and not pre-specified by the protocol. Of these, 104 had analyzable imaging data, 50 SBRT and 54 IMRT, with a mean baseline tumor size of 4.3 cm and 4.0 cm (p=0.17), respectively. Pancreatic tumor location included head (n=63), body (n=36), or other (n=5). There was no statistical significance between the mean percent change of tumor size between SBRT (-13.3%) and IMRT (-10.8%; p=0.834). Both arms had similar RECIST partial response (approximately 18% of patients) after treatment. Patients with analyzable CA 19-9 tumor marker data (14 SBRT, 17 IMRT) showed no significant difference in percent change (mean, 9.8%±111%, -40.7%±40%; p=0.262). The SBRT subgroup had significantly less patients drop-out due to clinical deterioration (1 SBRT, 9 IMRT; p=0.025) and experience any AE (26 SBRT, 49 IMRT; p=0.014), gastrointestinal AE (10 SBRT, 33 IMRT; p<0.001), grade 3 or higher AE (6 SBRT, 20 IMRT; p=0.017), and serious AE (2 SBRT, 10 IMRT; p=0.045) p=0.014, 0.017, 0.045, respectively). The main AEs and serious AEs were gastrointestinal events. Conclusions: When compared to IMRT, SBRT demonstrates improved tolerability for treatment of patients with LAPC with comparable clinical efficacy. Clinical trial information: NCT03257033 .

Short-course radiotherapy in rectal cancer: A single-center experience in Argentina.

146 Background: Short-course radiotherapy (SCRT) is an option in the neoadjuvant setting of resectable stage II-III rectal cancer, as well as in stage IV disease for local control without delay to initiate systemic treatment. Short-course radiotherapy is reported to be a comparable strategy for locally advanced rectal cancer. Limited data exist regarding the use of short-course radiation therapy when used as part of a non-surgical watch and wait approach. Methods: This is a retrospective analysis of all patients that underwent SCRT for rectal cancer at the Alexander Fleming Institute from 3/2014 to 6/2022. Results: 44 patients were treated with SCRT, 29 (66%) were male, with a median age of 59 years (46-73). Most of the patients had stage IV disease (26, 59,1%) followed by clinical stage II-III (18, 40,9%). 30 (68%) were localized in the middle with 14 (32%) in the lower rectum, by MRI imaging. In locally advanced disease 5/18 had T4 disease and 7/18 had N≥2. 14/18 patients (89%) underwent SCRT followed by consolidation chemotherapy (ChT) and 4 (11%) had induction ChT followed by SCRT. In metastatic disease 14/26 patients (53.84%) underwent SCRT followed by consolidation ChT, 10 (38.46%) had induction ChT followed by SCRT, and 2 (7.7%) received only SCRT. 29 (65.9%) of patients underwent surgery. 17/29(58.6%) had metastatic disease and 12/29 (41.4%) had locally advanced disease. Pathological response rates in operated patients were 2 (6.9%). 8 (18.2%) cases had a clinical complete response (cCR) (n=6 stage II-III and n=2 stage IV). Five (27.7% of the locally advanced group) patients with cCR underwent watch and wait with 1 local recurrence after 14 months. The remainder is disease free with a median follow-up time of 20 months (IC 95%: 15.14-24.85). Those that underwent SCRT following chemotherapy were more likely to have AEs compared to those that had chemotherapy following SCRT (11/30, 36.7% vs 25%, p=0.02). Conclusions: Our work shows that in a subgroup of patients diagnosed with LARC treated with SCRT followed by Chemotherapy, surgical treatment could be deferred after achieving a complete clinical response. The shorter time involved by SCRT allowed for less treatments with similar toxicity to long-course treatment regimens. SCRT is a reasonable option for local disease control in stage IV disease.

Dysphagia and shortness-of-breath as markers for treatment failure and survival in oropharyngeal cancer after radiation

BackgroundPost-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established. MethodsThis prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main outcome was overall survival (OS), and the secondary outcomes were local, regional, and distant disease control. ResultsThe majority of patients (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9–42.1). Univariable analysis showed significant associations between OS and all three symptoms of swallowing, choking, and shortness-of-breath. A composite variable integrating scores of all three symptoms was significantly associated with OS on multivariable Cox regression (p = 0.0018). Additionally, this composite symptom score showed the best predictive value for OS (c-index = 0.75). Multivariable analysis also revealed that the composite score was significantly associated with local (p = 0.044) and distant (p = 0.035) recurrence/progression. Notably, the same significant associations with OS were seen for HPV-positive only subset analysis (p < 0.01 for all symptoms). ConclusionsQuantitative patient-reported measures of dysphagia and shortness-of-breath 3-to-6 months post-treatment are significant predictors of OS and disease recurrence/progression in OPC patients and in HPV-positive OPC only.

Impact of Lymph Node Dissection on Survival After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group. Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20. Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local diseasecontrol. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

Application of anatomy unit resection surgery for lateral basicranial surgical approach in oral squamous carcinoma

BackgroundThe basicranial region lacks definite boundaries and includes various anatomical units. We developed a novel concept of the posterior oral anatomical complex (POAC) to identify these anatomical units in the basicranial region. OSCC with POAC involvement is termed posterior oral squamous cell carcinoma (POSCC) with poor prognosis. The principal aim of this study was to evaluate the effect of anatomy unit resection surgery (AUSR) on patients with POSCC.MethodsA total of 120 POSCC patients who underwent radical surgical treatment were recruited for this study. These POSCC patients were treated with conventional surgery or AUSR. According to the extent of primary tumor resection in the AUSR group, the lateral basicranial surgical approach can be subdivided into four types: face-lateral approach I, face-lateral approach II, face-median approach or face-median and face-lateral combined approach. Facial nerve function was evaluated according to the House-Brackmann Facial Nerve Grading System.ResultsThe overall survival rate was 62.5% and 37.5% in the AURS group and conventional group (hazard ratio: 0.59; p < 0.0001), respectively. The disease-free survival rate was 62.5% and 34.3% in the AURS group and conventional group (hazard ratio: 0.43; p = 0.0008), respectively. The local disease control rate in the AURS group (71.4%) was significantly better than that in the conventional group (34.4%) in present study (p < 0.0001). Compared to the conventional group, all the patients undergoing AURS were classified as T4 stage and presented with more lymph node metastasis (71.4%). A total of 20 patients (face-lateral approach I and face-lateral combined approach) were temporarily disconnected from the temporofacial branch of the facial nerve. Fifteen patients exhibited slight paresis, and five patients presented with moderate or severe paresis. The survival rate of zygomatic arch disconnection was 94.6% (54 of 56 patients).ConclusionThis lateral basicranial surgical approach based on AUSR improves the survival rate and enhances the local control rate while also preserving a good prognosis without damaging the nerve and zygomatic bone. This surgical approach based on AUSR provides a novel and effective surgical treatment to address POSCC with better prognosis, especially for patients without metastatic lymph nodes.

Natural history and treatment outcome of radiotherapy for Kimura's disease.

Kimura's disease is a rare inflammatory disease that usually appears in head and neck region. We reported natural history of the disease and treatment outcome of radiotherapy (RT) in Chiang Mai University Hospital. A retrospective review was performed for all Kimura's disease patients treated with radiotherapy at our center between 2002 and 2017. A total of 20 patients with Kimura's disease were reviewed. There were 14 men and 6 women. All patients presented with the mass in head and neck region. Eleven patients were treated with a definitive intent with RT, 9 patients were treated with RT after recurrence from other modalities. All patients were treated with local external beam RT with 2 Gy per fraction to a median total dose of 30 Gy (range 30-40). The median follow-up time was 4 years (range 1-16.5 years). One patient died from HIV opportunistic infection after 1.5 year of radiation with complete response of Kimura's disease. Most of the patients responded to radiotherapy and controlled the disease at the time of analysis. Two patients had multiple recurrences at new areas outside radiotherapy field. Skin toxicity grade 1 was the most common late side effect which was found in 8 (44%) patients. We did not find severe late toxicity or second malignancy in this patient cohort. : Good local control of Kimura's disease can be achieved, with a radiation dose of 30-40 Gy, with insignificant late toxicities. We suggest that radiotherapy should be one of the treatments of choice for Kimura's disease both in primary or recurrence setting.

TACE Combined with Lenvatinib and Camrelizumab for Unresectable Multiple Nodular and Large Hepatocellular Carcinoma (>5 cm).

The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC. We aimed to evaluate the safety and efficacy of TACE combined with lenvatinib and camrelizumab to treat unresectable multiple nodular and large HCC (>5 cm). Between November 2018 and June 2021, we retrospectively recruited 82 patients with unresectable multiple nodular and large HCC (BCLC stage B or C with a single nodular diameter of >5 cm). Of the patients who had not previously been treated, 33 patients received TACE + lenvatinib + camrelizumab (group A, TLC), and 49 patients treated with TACE + lenvatinib (group B, TLB) as the initial treatment. Related efficacy and safety results were recorded and assessed. The median follow-up periods of groups A and B were 14.5 ± 7.9 months (range, 3-36) and 12.5 ± 8.2 months (range, 3-32), respectively (P = 0.799). The progression-free survival (PFS) of groups A and B was 9.4 months and 5.9 months (P < 0.01), respectively, and overall survival (OS) was significantly longer in group A (16.4 months vs 11.0 months, P < 0.01). In group A, the local response rate (LRR) and disease control rate (DCR) were 51.5% and 81.8%, respectively, which was higher than the corresponding 46.9% and 77.6% observed in group B (P = 0.233; 0.429). Patients with BCLC B stage had better PFS and OS (P < 0.05). The BCLC stage was an independent factor that affected PFS and OS. There were no massive bleeding or treatment-related deaths. In patients with unresectable multiple nodular and large HCC (single nodular diameter of >5 cm), TACE combined with target therapy and immunotherapy is safe and effective.

Comparative Study between conventional EBRT alone and EBRT followed by intraluminal brachytherapy in local advanced cancer esophagus

Aim: The purpose of this study is to compare local tumor control, dysphagia-free survival, and complication in patients with locally advanced carcinoma esophagus using external beam radiotherapy (EBRT) alone (Arm A) and EBRT followed by intraluminal brachytherapy (ILBT) (Arm B). Materials and Methods: A total of 50 histopathologically proven patients of locally advanced unresectable cancer esophagus were taken for the study from March 2019 to February 2020 and were divided into two arms, 25 patients each. Arm A was treated by standard concurrent chemotherapy–radiotherapy (CTRT) alone (a total dose of 50 Gray (Gy) in 25 fractions (fr), 2 Gy/fr administered daily 5 days per week with weekly injection cisplatin 40 mg/m2) and Arm B received 44 Gy through two definitive radiation therapies along with computed tomography followed by ILBT (5 Gy/fr; 2 fr 1 week apart). Assessment was done weekly during RT and 3 and 6 months post treatment for local control of disease and dysphagia-free survival and complication. Results: The local tumor control was observed 80% and 84% at 6 months in Arm A and Arm B, respectively (P = 0.82). Six-month dysphagia-free survival was 52% versus 68% (P = 0.248) and stricture formation was found 16% and 24% (P = 0.479) in Arm A and Arm B, respectively. Conclusion: This study shows comparable results of CTRT-ILBT over CTRT alone in locally advanced esophageal cancer patients.

Harnessing immunotherapy to enhance the systemic anti-tumor effects of thermosensitive liposomes.

Chemotherapy plays an important role in debulking tumors in advance of surgery and/or radiotherapy, tackling residual disease, and treating metastatic disease. In recent years many promising advanced drug delivery strategies have emerged that offer more targeted delivery approaches to chemotherapy treatment. For example, thermosensitive liposome-mediated drug delivery in combination with localized mild hyperthermia can increase local drug concentrations resulting in a reduction in systemic toxicity and an improvement in local disease control. However, the majority of solid tumor-associated deaths are due to metastatic spread. A therapeutic approach focused on a localized target area harbors the risk of overlooking and undertreating potential metastatic spread. Previous studies reported systemic, albeit limited, anti-tumor effects following treatment with thermosensitive liposomal chemotherapy and localized mild hyperthermia. This work explores the systemic treatment capabilities of a thermosensitive liposome formulation of the vinca alkaloid vinorelbine in combination with mild hyperthermia in an immunocompetent murine model of rhabdomyosarcoma. This treatment approach was found to be highly effective at heated, primary tumor sites. However, it demonstrated limited anti-tumor effects in secondary, distant tumors. As a result, the addition of immune checkpoint inhibition therapy was pursued to further enhance the systemic anti-tumor effect of this treatment approach. Once combined with immune checkpoint inhibition therapy, a significant improvement in systemic treatment capability was achieved. We believe this is one of the first studies to demonstrate that a triple combination of thermosensitive liposomes, localized mild hyperthermia, and immune checkpoint inhibition therapy can enhance the systemic treatment capabilities of thermosensitive liposomes.

Ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma: a prospective study

PurposeThis single-arm, prospective, exploratory study investigated the effectiveness of ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma (OAL).Patients and methodsPatients with pathologically confirmed ocular adnexal low-grade non-Hodgkin lymphoma (predominantly mucosa-associated lymphoid tissue, MALT or follicular lymphoma) were included and treated with ultra-low-dose radiotherapy consisting of 2 successive fractions of 2 Gy at our institution between 2019 and 2021. Disease response was assessed clinically and radiographically within 4 months and at 3 to 6-month intervals after treatment. Data collected included rates of overall response, complete response (CR), partial response (PR), lesion size, and acute/chronic ocular toxic effects.ResultsSixteen patients with median age of 63 years (range 23–86 years) were included in the study. The histological subtypes included MALT (11 patients; 69%); follicular lymphoma (2 patients; 12%); Lymphoid hyperplasia (3 patient, 19%). At a median follow-up time of 15.5 months (range 5.0–30.0 months), the overall response rate was 88%, with a CR rate of 75% (n = 12) and a PR rate of 13% (n = 2). The average lesion area was reduced from 117.9 ± 60.4 mm2 before radiation therapy to 38.7 ± 46.0mm2 at initial evaluation post radiation therapy (P = 0.002, n = 16), and to 8.5 ± 21.2 mm2 (P < 0.001 compared with postoperative lesion area) in patients with response at one year (n = 11). Disease progression was noted in 2 patients (12%). The 1-year rates of local progression-free survivals (LPFS) and overall survival (OS) were 85% and 100%, respectively. No distant relapses were observed in any of the patients. No acute or late toxic effects were noted.ConclusionUltra–low-dose radiotherapy in patients with OAL is associated with excellent local disease control and long-term survival with no significant acute or late toxicities.

CARCINOMA GALLBLADDER: A REVIEW ARTICLE

Gallbladder cancer (GBC) is the third most common cancer of the gastrointestinal tract malignancies worldwide. Due to bad prognosis associated with the aggressive nature of the tumor, deficiency of sensitive screening evaluating tools for timely detection give rise to late diagnosis at advanced stage. The only curative treatment for gallbladder malignancy is surgical resection. This article supplements to the body of former literature in GBC to augment understanding of this rare but surely a curable disease. Carcinoma gallbladder having Stage I and II is unquestionably resectable with therapeutic goal. But, because of high percentage of recurrence, adjuvant therapy comes in combined form of chemotherapy plus radiotherapy. Chemotherapy regimens using gemcitabine have revealed a better effectiveness over 5 fluorouracil (5- FU) regimens. In order to improve the local disease control and to decrease the distant recurrences it is better if combination of radiotherapy and chemotherapy is given in the patients where it is achievable. Various molecular variations can be used as a marker for the gallbladder cancer, and Several molecular changes are detected in gallbladder cancer, but yet it is difficult to find out the ones which are the predominate one or directs the neoplastic process and to differentiate them from the other non-dominated genes. Immunotherapy is a form of therapy that promotes the immune system of an individual to identify and destroy the cancer cells that cannot be tackle by the surgery or have widely metastasized. Currently chemotherapy is the mainstay treatment for patients with advanced GBC. Similar to the immunotherapy, target therapy is used to treat the carcinoma gallbladder that is beyond the scope of surgery and have widely spread, they precisely target certain mutations that makes the tumour cell different from the normal healthy cells.

Limited parotid surgery as sole form of treatment for carefully selected malignant tumours of the parotid gland: Still sufficient on the long-term?

BackgroundThe aim of the study was to investigate the oncological and functional outcome following extracapsular dissection as the sole form of treatment in locally limited low-grade malignant parotid tumours in the long term. MethodsThe records of all patients treated for T1-T2 low-grade malignant tumours of the parotid gland solely by means of extracapsular dissection between 2005 and 2017 were studied retrospectively. ResultsA total of 16 cases formed our study sample (7 men, 9 women). Their mean age was 50.2 years (21–84 years). Mean follow-up was 107 months (60–201 months). In 6 cases the tumour was an acinic cell carcinoma, in 9 cases a mucoepidermoid carcinoma and in one case a basal cell adenocarcinoma. Regarding the T category, the tumour was Tis in one case, T1 in 12 cases and T2 in three cases. The five-year disease-specific survival rate was 100 %, as was local disease control. Facial nerve function was House-Brackmann grade I without exception. ConclusionsOur study showed very encouraging long-term results following primary extracapsular dissection as the sole surgical therapy for carefully selected low-stage, low-grade, inferiorly located lesions in patients with high compliance. Lay summaryThe “one-size-fits-all” strategy of complete parotidectomy with neck dissection might be tantamount to overtreatment by less aggressive cases of parotid cancer. Extracapsular dissection seems to be oncologically sufficient for carefully selected T1-T2 low-grade cases in the long-term in patients with ensured follow-up.

Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma-Tumor and Treatment Characteristics and Early Clinical Outcomes.

To report dosimetric characteristics and early clinical outcomes in patients with pelvic Ewing sarcoma undergoing particle therapy. Patients ≥ 18 years old with pelvic Ewing sarcoma treated in adjuvant or definitive settings were considered for this retrospective analysis. Proton therapy was carried out with 45-60 Gy (RBE) (1.5-2 Gy (RBE) per fraction) and carbon ion therapy for recurrent disease with 51 Gy (RBE) (3 Gy (RBE) per fraction). Local control (LC), disease control (DC) and overall survival (OS) were calculated using the Kaplan-Meier method. For our sample, 21 patients were available, 18 of whom were treated for primary, 3 for locally recurrent and 16 for inoperable disease. The median CTV and PTV were 1215 cm3 and 1630 cm3. Median Dmean values for the PTV, bladder and rectum and median V40 Gy for the bowel for patients undergoing proton therapy were 56 Gy (RBE), 0.6 Gy (RBE), 9 Gy (RBE) and 15 cm3, respectively. At the end of particle therapy, G 1-2 skin reactions (n = 16/21) and fatigue (n = 9/21) were the main reported symptoms. After a median follow-up of 21 months, the 2-year LC, DC and OS were 76%, 56% and 86%, respectively. Particle therapy in adult pelvic Ewing sarcoma is feasible and provides excellent dosimetric results. First clinical outcomes are promising; however, further long-term follow-up is needed.

SURG-04. CDK2NA/B, SMAD4, AND PIK3R1 MUTATIONS ARE ASSOCIATED WITH INCREASED RISK OF LOCAL RECURRENCE AFTER SURGICAL RESECTION OF BRAIN METASTASES

Abstract BACKGROUND While resection of brain metastases (BMs) offers favorable local disease control, factors and genetic alterations associated with local recurrence are not well defined. This study examined patient, tumor, treatment, and genetic factors associated with local recurrence. METHODS A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical outcome and genetic data available. Local recurrence was the primary outcome of the study. Next-generation sequencing of coding regions in over 500 cancer genes was performed to detect mutations. Cox proportional hazards analysis was performed to identify patient, tumor, treatment, and genetic factors associated with local recurrence. RESULTS We identified 91 patients who underwent surgical resection of a BM with available data, of which 80 (87.1%) underwent preoperative radiotherapy or received some form of adjuvant radiation to the resection cavity. Primary pathologies in the cohort included non-small cell lung cancer (24.2%), melanoma (24.2%), breast cancer (16.5%), gastrointestinal cancers (13.2%), gynecologic cancers (4.4%), renal cell carcinoma (4.4%), and other cancers (13.2%). Eleven patients (12.1%) developed postoperative recurrence at the surgical site with 6- and 12-month PFS of 91.2% and 84.2%. Multivariate Cox proportional hazard analysis identified cancer type (Gyn and RCC vs Others: OR 39.4, p=0.002), CDK2NA/B co-deletion (OR 37.52, p=0.0009), PIK3R1 mutation (OR 56.88, p=0.003), and SMAD4 mutation (OR 134.8, p=0.0007) to be associated with time to local recurrence. Overall survival and length of follow-up were not different based on mutational status of these genes, demonstrating that results were not due to survival bias. CONCLUSIONS Genetic alterations within BMs impact clinical outcomes after surgical resection. Further work is needed to determine if targeted therapies for BMs with these alterations can decrease rates of local recurrence.

Stereotactic body radiotherapy in oligoprogressive metastatic castration-resistant prostate cancer during abiraterone or enzalutamide.

This monocentric, single-arm, retrospective study investigated the role of stereotactic body radiotherapy in patients with metastatic castration resistant prostate cancer who experienced oligoprogression during androgen receptor targeted agents. We retrospectively enrolled metastatic castration resistant prostate cancer patients treated with androgen receptor targeted agents between December 2016 and January 2022. All patients experienced an oligoprogression (defined as the appearance and/or the progression of ⩽5 bone or nodal or soft tissue metastases) during treatment with androgen receptor targeted agents and received stereotactic body radiotherapy upon oligoprogressive sites, preserving the androgen receptor targeted agents. Further stereotactic body radiotherapy upon new metastatic sites was permitted. Patients showing visceral metastases or receiving palliative radiotherapy were excluded. Progressive disease at >5 metastatic sites or the appearance of visceral metastases led to a change of the systemic treatment. Primary endpoints were 36-month survival rate and 36-month rate of patients receiving treatment with androgen receptor targeted agents. Secondary endpoints were local disease control, biochemical response and safety. We analyzed data from 30 patients. The 36-month survival rate was 90% (27 patients); 36-month rate of patients who were still on treatment with androgen receptor targeted agents was 50%. 20 of 30 patients had performed imaging control after a single course of stereotactic body radiotherapy: overall response rate was 50%, while clinical benefit was 93%. No ⩾G2 adverse events related to stereotactic body radiotherapy were recorded. Stereotactic body radiotherapy in oligoprogressive metastatic sites during androgen receptor targeted agent treatment resulted in a feasible and effective treatment to delay the start of next-line systemic treatment and prolong overall survival in metastatic castration resistant prostate cancer. Longer follow-up and further prospective studies are necessary to confirm our preliminary results.

Conservative surgery with microwave ablation for recurrent bone tumor in the extremities: a single-center study

BackgroundSurgical treatment for recurrent bone tumors in the extremities still presents a challenge. This study was designed to evaluate the clinical value of microwave ablation in the treatment of recurrent bone tumors.MethodsWe present 15 patients who underwent microwave ablation for recurrent bone tumors during the last 7 years. The following parameters were analyzed for outcome evaluation: general condition, surgical complications, local disease control, overall survival, and functional score measured using the Musculoskeletal Tumor Society (MSTS) 93 scoring system.ResultsPercutaneous microwave ablation in one patient with osteoid osteoma and another with bone metastasis resulted in postoperative pain relief. Thirteen patients received intraoperative microwave ablation before curettage or resection, including those with giant cell tumors of bone (6), chondroblastoma (2), osteosarcoma (2), undifferentiated sarcoma (1), and bone metastases (2). All patients achieved reasonable local tumor control in the mean follow-up of 29.9 months. The functional score was 24.1 for the 15 patients 6 months after the operation. Four patients had tumor metastasis and died, whereas 3 patients with tumors survived, and the remaining 8 patients without the disease survived.ConclusionsMicrowave ablation represents an optional method for local control in treating recurrent bone tumors in the extremities.

Meta-Analysis of Repeat Hepatectomy versus Radiofrequency Ablation for Recurrence of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and a leading cause of cancer-related death in both the developed and developing world. Recurrent HCC (rHCC) develops in a significant proportion of patients even following curative-intent resection. In the absence of a structured treatment algorithm, a number of treatment options including repeat hepatectomy (RH) and radiofrequency ablation (RFA) have been utilized in select patients with rHCC. The aim of this systematic review and meta-analysis was to compare short- and long-term outcomes of patients undergoing RHR versus RFA for rHCC. Four electronic databases were screened until September 2022. A total of 17 studies were included in the meta-analysis. Overall and disease-free survival were comparable among the two groups. Patients undergoing RH were less likely to develop a second recurrence (RR 0.89, 95% C.I. 0.81 to 0.98, p = 0.02). Overall and major morbidity were significantly increased in the RH group (RR 3.01, 95% C.I. 1.98 to 4.56, p &lt; 0.001 and RR 3.65, 95% C.I. 2.07 to 6.43, p &lt; 0.001, respectively), while mortality was similar between RFA and RH. The data demonstrated that RFA is a safe and efficient alternative to RH for selected patients with rHCC. Nevertheless, despite higher morbidity associated with RH, repeat resection remains the preferred treatment option whenever feasible, as it allows for better local disease control.

Particle beam radiation therapy for head and neck rhabdomyosarcoma in adults

Rhabdomyosarcoma (RMS) is rare in adults, with a significantly worse prognosis than its pediatric counterpart. Radiotherapy (RT) plays a significant role in treating head and neck RMS (HNRMS), but the outcomes of conventional RT are limited by the complex anatomy and unfavorable pathology subtypes of the adult H&N RMS. Here, we aim to report the effectiveness and safety of carbon-ion beam RT (CIRT), either alone or in combination with proton radiotherapy (PRT) in the management of adult HNRMS. Fifteen adult patients with HNRMS were enrolled on a prospective registry protocol between 06/2015 and 12/2019. Eight patients presented with parameningeal tumors, and eight had unfavorable pathology subtypes [alveolar =7, not otherwise specified (NOS) =1]. Eleven patients had gross tumors before the start of RT (volume range, 46.1-137.6 cm3). Two patients failed the earlier RT. All except for one patient received multi-drug chemotherapy. The median absolute dose of particle beam RT was 70.0 Gy [relative biological effectiveness (RBE)]. With a median follow-up of 21 months, local or distant recurrence occurred in three and four patients, respectively, and two added patients had both local and distant failure. One patient died of distant metastasis (DM), and another died of an unrelated condition. The 1- and 2-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 87.5% and 70.0%, 92.3% and 67.1%, 72.2% and 54.2%, and 65.0% and 24.4%, respectively, for the entire cohort. Both patients who failed earlier RT and received salvage CIRT developed DM but were alive at last follow-up. No acute toxicity of ≥ grade 3 or late toxicity of ≥ grade 2 was observed. CIRT, either used alone or in combination with PRT, is not only feasible and safe but also useful in local disease control for HNRMS. DM is the most important cause of treatment failure; thus, more effective systemic treatment is needed to improve the prognosis of HNRMS further.