Oligometastasis Research Articles

Survival outcomes of esophageal cancer patients with recurrence after curative treatments

BackgroundLittle is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM).MethodsEC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS).ResultsIn total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P < 0.01). Surgical treatments provided significantly better survival outcomes than CRT or chemo-/radiotherapy alone (3-year overall survival (OS); 78.1% vs. 42.5% vs. 28.9%, P < 0.01), mainly due to prolonging survival after the recurrence (3-year PRS 62.9% vs. 16.7% vs. 16.2%, P < 0.01). Multivariable analysis focusing on patients with OM revealed cStage III-IV disease (P < 0.01), high GPS at the time of recurrence (P = 0.02) and non-curative treatments (P < 0.01), to be independently associated with poor PRS. In contrast, in patients with NOM, no independent predictors for poor PRS were identified.ConclusionsThe survival outcomes of patients with relapsed EC remain poor. Surgical treatments could provide survival benefits for patients with recurrent EC, especially for patients with OM.

Contralateral axillary lymph node metastasis in breast cancer: An oligometastatic-like disease

BackgroundContralateral axillary lymph node metastasis (CAM) is rare. It remains controversial whether CAM should be regarded as a regional or distant metastatic disease. Our study aims to investigate the accurate clinical orientation and management of CAM. MethodsTwo hundred and ninety-nine female patients diagnosed with breast cancer from 2000 to 2014 and confirmed to develop CAM, oligometastasis (OM) or locoregional recurrence (LRR) at Fudan University Shanghai Cancer Center (FUSCC) were included in this study. Baseline information and survival outcomes were analyzed and compared among the three groups. ResultsPatients with CAM exhibited similar overall survival (OS) and progression-free survival (PFS) to those with OM, but worse than those with LRR (HR: 0.47 [95 % CI: 0.27–0.85], p = 0.0097; HR:0.39 [95 % CI: 0.24–0.63], p < 0.0001, respectively). Considering the patients presented with CAM or OM as a whole, we found that local treatment combined with systemic treatment did not provide a superior survival benefit over systemic treatment alone. ConclusionCAM was similar to an oligometastatic-like disease, and patients with these diseases may benefit from systemic treatment. Adding local treatment failed to significantly improve OS.

Patients with metastatic renal cell carcinoma who receive immune-targeted therapy may derive survival benefit from nephrectomy

BackgroundNephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy.MethodsPatients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed.ResultsWith a median follow-up time of 29.3 months (95% CI 28.5–30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3–13.3) and 14.4 months (95% CI 12.6–16.2), respectively, as well as an HR of 0.476 (95% CI 0.323–0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors.ConclusionsNephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group

Background and purposeThe apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. Materials and methodsNine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0–500 vs. 150–500 s/mm2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CVD) and calculation methods (CVC). Absolute ADC differences between calculation conditions were evaluated using Friedman’s test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. ResultsThe median (range) CVD and CVC were 0.06 (0.02–0.32) and 0.17 (0.08–0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CVC to 0.04 (0.01–0.16). CVD was comparable between ROI types. ConclusionOverall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations.

Outcomes of early onset colorectal cancer (EOCRC) with synchronous liver oligometastasis.

e15599 Background: Screening and removal of pre-malignant adenomas has reduced CRC incidence in adults older than 50 years (later onset CRC [LOCRC]), but EOCRC incidence has increased by 1-2% annually since the 1990s. The liver is the commonest site of CRC metastasis, and EOCRC presents with more advanced stage compared with LOCRC. Oligometastasis (OM) refers to potentially resectable CRC, and complete resection of CRC primary and OM is associated with improved survival and potential cure. Here, we examined treatment outcomes of EOCRC with synchronous liver oligometastases (sLiOM) at our institution. Methods: We performed a retrospective review of institutional electronic health records and identified 160 EOCRC patients with sLiOM treated with curative intent in the last decade. Demographics, treatment, and follow up data were recorded, and analysis for survival outcomes performed. The study protocol was exempt after review by Mayo Clinic institutional review board. Results: Of 160 patients, median age at diagnosis was 43 years. Primary tumor was in the left colorectum in 73% and right colon in 26% of patients. Metastasis was limited to the liver only in 64%, and liver metastasis was solitary in 14% of patients (table 1). Fluoropyrimidine doublet backbone (81%) was more commonly used compared to triplet (19%), with doublet + bevacizumab (41%) as the most common regimen. Hepatectomy only (59%), combined hepatectomy with ablation (32%), ablation only (5%), transarterial radioembolization (2%), and trans arterial embolization (1%) were the modalities employed for sLiOM. Of the 148 patients who underwent hepatectomy, R0 resection was achieved in 51%. After a median follow-up of 37 months, progression-free survival was 11.6 mos (95% CI 9-14mos) and median overall was 83.6 mos (95% CI 62-105mos). The median time to liver progression was 16 mos (95% CI 12-20 mos). At data cut off, 41 patients (26%) were alive and disease-free, and 60 patients (38%) were alive and disease free in the liver only. Conclusions: This multi-site, retrospective analysis of EOCRC patients demonstrates excellent survival outcomes with localized treatment of sLiOM. Median OS in this cohort compares favorably to previously reported mOS of 36 months in EOCRC patients (Arhin et al, 2021). Cure is not often achieved even after treatment of sLiOM in this cohort, suggesting aggressive disease biology and the need for improved patient selection. [Table: see text]

Therapy results of patients with metastatic castration‑resistant prostate cancer. Regional experience

Purpose of the study. To evaluate the results of first‑line treatment in patients with metastatic castration‑resistant prostate cancer (mCRPC).Patients and methods. The evaluation of own clinical observations of 25 patients with mCRPC for the period from July 2014 to July 2021 by random sampling is given. Patients are divided into the ISUP group, the status of the initial treatment, and the type of previous treatment. Therapy was determined by the nature of progression. The following drugs were used as therapeutic agents: docetaxel, enzalutamide, abiraterone acetate + prednisolone, strontium (89 150 mBq). Results evaluation was carried out by RECIST 1.1. criteria. Statistical data processing was carried out using programs SPSS Statistica 2.0.Results. When assessing the tumor response to the therapy in 2 (8 %) patients, a complete therapeutic response was obtained, partial was registered in 4 (16 %) cases, stabilization in 9 (36 %), progression in 10 (40 %). The main response was stabilization and partial response, which was noted in 13 (52 %) patients. On 11 (44 %) patients with bone metastases as the cause of mCRPC, enzalutamide showed the best effect. Patients with lymph node metastases 3 (12 %) had a partial and complete response with a combined treatment regimen – lymphadenectomy + enzalutamide. In the group of patients n = 9 (36 %) – metastases to lymph nodes and bones, the best effect in the form of stabilization and partial response in enzalutamide. In 1 (4 %) patient with visceral progressing metastatic pleural lesion. Two patients had passed away by the end of the research.Conclusion. Enzalutamide and abiraterone showed the best responses in metastatic bone damage (as the cause of mCRPC). We observed more than 50 % of stabilizations during enzalutamide treatment. Combined treatment regimens should be used among patients with only metastatic lymph node lesion (oligo metastasis): this makes it possible to achieve a complete response and a greater number of stabilizations in some patients.

Hormone Positive HER2 Negative Breast Cancer Metastatic to the Rectum: A Case Report

Background: The rectum is an uncommon site for metastases from Invasive Ductal Carcinoma (IDC) of the breast, and it poses risks such as perforation and obstruction.&#x0D; Case Report: A 50-year-old non-diabetic, non-alcoholic, and nonsmoker premenopausal female patient diagnosed with rectal metastasis primarily originating from breast cancer.&#x0D; In 2009, the patient was diagnosed with stage IV hormone positive, Her-2 (+2) negative, FISH positive right breast cancer with cervical (C6) vertebrae metastasis seen on PET scan. As she had oligo metastasis with a single bony focus, she was treated with intent to cure. For this purpose, she received radiation therapy to the cervical vertebrae, resulting in a complete response. This was followed by pseudo-neoadjuvant chemotherapy with six cycles of Docetaxel and trastuzumab. The patient then underwent a right-modified radical mastectomy. The pathology showed no complete response with residual 2.5 cm invasive carcinoma (PT2), and 4 out of 25 Axillary lymph nodes were positive for metastases (PN2). She was given (pseudo) adjuvant radiotherapy to the chest wall and lymphatics and was started on (pseudo) adjuvant tamoxifen. Trastuzumab was completed for one year as a (pseudo) adjuvant setting.&#x0D; Her disease seemed to be cleared up as no new cancer signs were reported by follow-up full body scans (CT/PET). After seven years, in May 2016, her PET-CT scan showed multiple new hypermetabolic osseous lesions, in keeping with metastasis involving the right shoulder, mid-thoracic spine, left aspect of L5, right sacrum, and the greater trochanteric region of the left femur and left ischium. She also presented a new hypermetabolic retroperitoneal paracaval lymph node, in keeping with metastasis. The new ill-defined hypodensity in the left hepatic lobe was associated with increased FDG uptake, which is suspicious for early metastasis. She also presented a tiny right lung peri-fissural nodularity that was too small to be characterized by PET.&#x0D; She was treated with Zoladex 3.6 mg injection monthly, Femara 2.5 mg daily, Palbociclib 125 mg PO daily for 21 days over a 28-day cycle, and Denosumab 120 mg monthly. The treatment was initiated in Singapore. As previously stated, Her-2 testing was reported as negative. The patient went into complete remission for more than six years, as documented by the PET scan conducted on January 19, 2022. Later, in June 2022, the patient developed signs and symptoms of intestinal obstruction (abdominal pain, nausea, and vomiting) and was diagnosed with rectal cancer metastases of breast origin.&#x0D; Conclusion: As the patient first developed breast cancer with oligo-bony metastasis, which was successfully treated with chemotherapy and radiotherapy, but later relapsed in the lung, liver, lymph nodes, and multiple bony sites. She was treated successfully via hormonal and targeted therapy. Finally, she relapsed in the form of rectal metastasis.

Does Local Failure Following Oligometastasis-Directed SBRT Predict for Widespread Progression and Overall Survival?

<h3>Purpose/Objective(s)</h3> The potential of oligometastasis (OM)-directed therapy to translate to survival benefit has been shown in randomized trials, but typically in small or histology-specific cohorts (i.e., prostate or NSCLC). We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in a large, multi-institutional cohort of patients across heterogeneous histologies treated with SBRT to OMs. <h3>Materials/Methods</h3> Patients treated at 6 international centers from 2007 – 2016 were retrospectively reviewed and included if they had 1) five or fewer lesions, 2) no history of brain metastases, 3) curative treatment for primary disease, and 4) SBRT to all known OMs at initial presentation. The relationship between LC at certain time points and OS and WSP (>5 active/untreated lesions) were explored using Cox and Fine-Gray regression models. The relative strength of association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk. <h3>Results</h3> In total, 1033 patients treated to 1700 OMs were analyzed. The median follow up was 24.1 mo (range: 0.3-104.7). Most patients (57.1%) had solitary OM, 24.0% had 2 OMs, 10.3% had 3 OMs, and 8.6% had 4-5 OMs. The most common histologies were NSCLC (25.2%), colorectal (22.8%), prostate (12.8%), and breast (8.1%). The median prescription dose was 48 Gy (range: 10-60) in a median of 5 fractions (range: 1-15). Median OS was 44.2 mo. Cumulative incidence of local failure at 6m, 1y, 2y and 3y was 3.3%, 10.0%, 19.6% and 23.9% respectively. As detailed below, patients who fail locally in any or all SBRT-targeted OMs have significantly increased risk of WSP and death compared to those with no failure. These risks may be greater with shorter duration of LC. Patients who failed in only a subset of treated OMs and those who failed in all OMs did not have significantly different WSP and OS outcomes. Minimum BED to the GTV or ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax, across a range of simulated a/b ratios. <h3>Conclusion</h3> This large multi-institutional series demonstrates that duration of LC in SBRT-targeted OMs translates strongly to WSP and OS outcomes in an all or nothing manner, where failure in a subset of treated OMs appears no different in risk compared to failing in all OMs. This highlights the importance of maximizing LC to each OM in this treatment paradigm, where GTV or ITV Dmin may be a key dosimetric parameter.

A Prospective Multi-Institutional Observational Study on ER, PR, HER2/NEU, and Ki-67 Expression and Discordance Pattern in Primary and Metastatic and Recurrent Carcinoma Breast and Its Therapeutic Implications and Prognostic Outcome.

Only few studies reported in literature that has elucidated in detail the implications of molecular typing in metastatic and recurrent breast cancer. In this prospective study, we have analysed in depth the pattern of expression, discordances of molecular markers in various metastatic sites, and recurrent cases and their response to chemotherapy/targeted agents and the prognostic outcome. The primary aim of the study was to determine ER, PR, HER2/NEU, and Ki-67 from recurrent and metastatic carcinoma breast to study the expression pattern and discordance and also to study the degree of discordance in relation to the site of metastasis and pattern of metastasis (synchronous vs metachronous) and discordance pattern with the response to chemotherapy and median overall survival rates in months in available subset of patients. Prospective open-label study done at the Government Rajaji Hospital, Madurai Medical College, and Government Royapettah Hospital, Kilpauk Medical College, India, from November 2014 to August 2021. All breast carcinoma patients with recurrence or oligo metastasis (defined as one organ with less than 5 metastases in our study) with known receptor status were eligible and 110 patients were enrolled in the study. ER (ER + to ER -) discordance was seen in 19 (26.38%) cases. PR (PR + to PR -Ve) discordance was seen in 14 (19.17%) cases. HER2/NEU (HER2/NEU + Ve to -Ve) discordance was seen in 3 (16.6%) cases. Ki-67 discordance was seen in 54 (49.09%) cases. High Ki-67 as a proliferative marker has increased response to chemotherapy but earlier relapse and disease progression especially in Luminal B type. In further subset analysis, ER, PR, and HER2/NEU discordance is higher for lung metastasis (ER, PR 61.1%, p value .001, HER2/NEU 5.5%), followed by liver metastasis (ER, PR 50%, p value .0023, 1 case turning ER -ve to + ve, HER2/NEU 1 (10%)). In lung, discordance is more for metachronous metastasis. In liver, discordance is 100% for synchronous metastasis. Synchronous metastasis with discordance in ER and PR is associated with rapid disease progression. High Ki-67 subset of Luminal B-like tumors progressed rapidly than triple negative and HER2/NEU positive subset. Complete clinical response rate in contralateral axillary node metastasis group was 87.8%, followed by local only recurrence with high Ki-67 where chemotherapy had response rate of 81% and 2years DFS of 93.12% after excision. Certain subsets like contralateral axillary nodes and supraclavicular nodes which present as oligo metastatic disease with discordance and high Ki-67 respond well to chemotherapeutics and targeted agents improving the OS in this subset of patients. Molecular markers and their expression and discordance pattern determine the therapeutic outcome and prognosis of the disease. Early identification and targeting the discordance would go a long way in improving the outcome and DFS and OS of breast cancer patients.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (SMART) With Median Biologically Effective Dose of 100 Gy10 for Oligometastases

<h3>Purpose/Objective(s)</h3> Randomized data show an overall survival (OS) benefit of stereotactic ablative body radiation therapy (SABR) in addition to chemotherapy (CT) in selected patients with oligometastasis (OM). While ablative dose can be safely delivered to some lesions, others in proximity to some organs at risk (OARs) such as bowel may be treated with non-ablative dose to limit toxicity. Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting OARs, which may improve long-term disease control. <h3>Materials/Methods</h3> The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Patients with < 3 months (mo.) follow-up after SMART were excluded. Local control (LC), freedom from distant progression (FFDP), progression free survival (PFS), and OS were estimated using the Kaplan-Meier method. LC was evaluated using RECIST 1.1 criteria. Acute toxicity was defined as within 90 days of SMART and evaluated using CTCAE v4 criteria. <h3>Results</h3> 101 patients with 114 OM lesions were treated on a 0.35T-MR Linac at 2 institutions between 2018-2020. Median age was 62 years (range 23-89), and 99% were ECOG 0-1 performance status. The primary tumor was definitively managed in 34.7%, most commonly in the lung (30.7%), colon/rectum (22.8%), cervix/uterus/ovary (13.9%), or breast (5.9%). About 50% received CT for OM prior to SMART. SMART was delivered to 1 (87.7%) or 2 (10.5%) lesions, mostly involving abdominal/pelvic lymph nodes (40.4%), liver (17.5%), lung (17.5%), or adrenal gland (11.4%). All were treated without fiducial markers and with real-time tissue tracking and automated beam gating, typically in breath hold. The median prescribed RT dose was 45 Gy (range 24-60Gy) in a median 5 fractions (range 3-15). The median biologically effective dose (BED₁₀) was 100 Gy₁₀ (range 41.4-180). The median PTV was 14.5 cm³ (range 1.5-567.8). Median follow-up was 10 months (range 3-25) from SMART. One-year LC, FFDP, PFS, and OS were 88%, 38.2%, 36.1%, and 90.6%, respectively. Median PFS and OS were 9 months and not reached, respectively. No acute/late grade 3+ toxicities were recorded. <h3>Conclusion</h3> To our knowledge, this represents the largest analysis of SMART for OM. A median prescribed BED₁₀ of 100 Gy₁₀ resulted in excellent early LC and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. These outcomes are noteworthy given the predominance of OM, especially LNs, treated with dose escalation in proximity to gastrointestinal OARs; such lesions are notably underrepresented in SABR OM trials. Prospective evaluation of dose-escalated SMART for OM is warranted.

Guidelines for the diagnosis and treatment of pancreatic cancer in China(2021)

The incidence of pancreatic cancer has been rising worldwide,while its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Surgery Association,Chinese Society of Surgery,Chinese Medical Association updated "Guidelines for the diagnosis and treatment of pancreatic cancer in China （2021）" based on the Guideline of Management of Pancreatic Cancer in China which had been published in 2014. This updated guideline was formulated after reviewing evidence-based and problem-oriented literatures published from 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system. This guideline aims to improve the ability of clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and furtherly improve the prognosis of pancreatic cancer patients.

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

Abstract The incidence of pancreatic cancer has been rising worldwide, and its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Association, the Chinese Society of Surgery, Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014) after reviewing evidence-based and problem-oriented literature published during 2015–2021, mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer, conversion strategies for locally advanced pancreatic cancer, treatment of pancreatic cancer with oligo metastasis, adjuvant and neoadjuvant therapy, standardized processing of surgical specimens and evaluation of surgical margin status, systemic treatment for unresectable pancreatic cancer, genetic testing, as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues, and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. This guideline aims to standardize the clinical diagnosis and therapy, especially surgical treatment of pancreatic cancer in China, and further improve the prognosis of patients with pancreatic cancer.

Metastatic site-specific utilization and outcome of immunotherapy in stage IV melanoma: A national perspective.

e21525 Background: Metastatic melanoma is an aggressive disease with a rapid systemic dissemination. We evaluated the effect of metastatic sites on the utilization immunotherapy and survival outcomes in stage IV melanoma. Methods: The National Cancer Database from 2010-2017 was queried for stage IV melanoma. Those with missing relevant data were excluded. Patients were grouped into five categories based on metastatic sites: lung metastasis only, brain metastasis only, liver metastasis only, bone metastasis only and multiple sites metastasis. Multivariable logistic regression was used to predict use of immunotherapy. Effects of immunotherapy on overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards model. Results: A total 12, 315 were included in the study, among whom 2206 (17.9%) had lung metastasis only, 1,873 (15.2%) had brain metastasis only, 785 (6.4%) had liver metastasis only, 662 (5.4%) had bone metastasis only and 5,983 (48.6%) presented with multiple metastatic sites. Surgery at primary site was performed in 34.3% of patients with bone metastasis (p&lt;0.001), and radiation therapy was delivered to 69.2% patients with brain metastasis (p&lt;0.001). Site of metastatic disease was associated with immunotherapy utilization, with multiple sites (OR = 1.149, p=0.012), and distant lymph nodes (OR=2.867, p&lt;0.001) demonstrating the strongest association, while patients with oligo brain metastasis were less likely to receive immunotherapy (OR = 0.486, p&lt;0.001). Immunotherapy is associated with superior survival among metastatic melanoma patients (HR=0.433, P&lt;0.001). The Kaplan-Meier curves showed the median overall survival among the immunotherapy group was 33.7 months for lung metastasis (vs. 13.4 months without immunotherapy, HR=0.633, p&lt;0.001), 25 months for brain metastasis (vs. 6.7 months without immunotherapy, HR=0.447, P&lt;0.001), 16.8 months for liver metastasis (vs. 4.2 months without immunotherapy, HR=0.449, P&lt;0.001), 18.3 months in bone metastasis (vs. 7.6 months without immunotherapy, HR=0.615, p&lt;0.001) and 12.1 months in multiple metastasis (vs. 3.8 months without immunotherapy, HR=0.338, p&lt;0.001). Conclusions: Utilization of immunotherapy is influenced by location of metastatic disease in stage IV melanoma. Overall survival is improved for patients treated with immunotherapy.[Table: see text]

Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT: TROD 09-004 Study.

To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.

Oligometastases in head and neck carcinoma and their impact on management.

Historically, patients with head and neck squamous cell carcinoma (HNSCC) with distant metastases were regarded as palliative. Oligometastasis (OM) refers to patients with a limited number of distant metastatic deposits. Treatment of patients with OMs has been reported in patients with lung, colon, breast, prostate and brain malignancies. Selected patients with oligometastatic HNSCC have a higher probability of durable disease control and cure and these patients should be treated aggressively. Treatment options for patients with HNSCC OMs include single or combinations of the three arms of cancer treatment, that is surgery, radiotherapy and chemotherapy/immunotherapy. To date, there are limited studies reporting the management of OM with head and neck malignancy. This review will give insights into the management of OMs in HNSCC.

Radical Conformal Radiotherapy versus Two-Dimensional Radiotherapy in Oligometastatic Breast Cancer Patients: Response, Toxicity, and Survival

AbstractBackground: oligometastatic breast cancer patients achieved better progression-free survival without significant toxicity, so this urge patients subgroups identification who might gain more benefit from aggressive local therapy. In comparison to antro posterior, post anterior, and direct post anterior techniques, 3-dimensional conformal irradiation delivered for treatment of lumbar vertebrae metastasis was much better in the decrease of bowel and spinal cord exposure. Aim of the work: to evaluate clinical outcome gains achieved by 3D radiotherapy versus 2D radiotherapy in certain breast cancer patients with bony oligo metastasis with expected favorable survival.Methods: In a retrospective cohort, 60 patients were enrolled in 2D versus 3D arm. Treatment and survival outcomes were observed. Results: 3D radiotherapy offer a significantly better pain response, local control, and lower toxicity than patients were received treatment delivery by 2D radiotherapy with p-value = 0.004,0.002 and 0.004 respectively, patients were delivered 2D radiotherapy had shown a progressive disease than those treated by 3D radiotherapy of statistical significance p-value = 0.01. The 3D arm was better than the 2D arm in the term of better significant PFS and nonsignificant OS, p-value = 0.04, 0.14 respectively. Conclusion:3D conformal radiotherapy is of great value in the improvement of local control, pain response, progression-free survival, and overall survival with a tolerable toxicity profile in breast cancer patients diagnosed with bony oligo metastasis.Keywords; Conformal radiotherapy, 2-dimensional radiotherapy, oligometastatic, breast cancer

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis

The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies. To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT). Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively. Definitive SBRT. Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS. In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event. This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.

Survival and Patterns of Failure in Oligometastatic Esophagogastric Cancer

Metastatic esophagogastric cancer (EGC) has poor outcomes, with median overall survival (OS) of 9-11 months. Studies in other sites such as lung have shown improved survival with local treatment for oligometastasis (OM). However, there is very limited data on oligometastatic EGC. We investigated outcomes, prognostic factors, and patterns of first progression in patients with oligometastatic EGC. From 2008-2018, 1438 patients (pts) presented to our institution with stage IV EGC. Of these, 197 pts had OM (defined as ≤5 metastatic lesions, excluding primary) and were included for analysis. Median age was 67 years and most (77%) were male. 46 pts (23%) had gastric (GC) and 151 (77%) had esophageal/GE junction (GEJ) tumors. First progression was classified as limited to initial sites, new sites, or failure at both initial and new sites. OS was stratified by primary tumor site, number of OM, and sites of OM using Kaplan Meier and log rank tests. Cox proportional hazards model was used to investigate correlation between prognostic factors and outcomes. At a median follow up of 22.5 (1-117) months, median OS for the whole cohort was 25 months (95%CI: 22.6-27.4) with a statistically significant difference between GC and GEJ cancer (37 vs. 25 months, p = 0.03). Location of OM was as follows: non-regional nodes (44%), liver (17%), peritoneal nodules (7%), bone (6%), lungs (4%), brain (2%), liver plus non-regional nodes (5%), and other (15%). Peritoneal nodules were more common in GC whereas bone, lungs, and brain were more common in GEJ cancer. Most pts had a solitary OM (42.6%). The number or sites of OM did not correlate with OS. Of 152 pts who progressed, 91 (60%) had isolated initial site failure, 17% had isolated new site failure, and 23% had both initial and new site failure. 13% and 10% of pts underwent surgery for primary site and OM respectively. Radiation therapy (RT) to primary site (median 37.5 Gy in 15 fractions), was delivered to 37%, usually upon progression (57%). 11% received RT to OM. On univariate analysis, gastric primary, younger age, primary tumor or OM resection, RT to the primary, and isolated initial site failure were significantly associated with better OS. On multivariate analysis, age (HR: 1.031, p = 0.001) surgery to the primary (HR: 0.295, p = 0.002), and initial-site failure (HR: 1.4 p = 0.002) remained significantly correlated with OS. We observed a longer OS for oligometastatic EGC, compared to historical results for general metastatic disease reported in the literature. This suggests that EGC patients with OM are a prognostically distinct group and may benefit from tailored treatment strategies such as ablative local therapy. Most patients first progressed in their initial sites of disease, suggesting a role for local therapy earlier in the treatment course. Younger patients and those undergoing primary tumor resection had superior OS.

Linear accelerator-based stereotactic body radiation therapy in the treatment of oligometastatic disease.

The present study reports the clinical outcomes of hypofractionated stereotactic body radiation therapy (SBRT) for oligometastasis (OM) originating from various tumors. Between February 2012 and April 2017, 40 patients with unresectable OM were treated with SBRT. Of these patients, 92% showed a solitary nodal metastasis and the rest had up to three metastases. The dose prescription was 50 Gy in 10 fractions with three-dimensional conformal techniques or volumetric intensity-modulated arc therapy. Median follow-up was 14 months. Of the 40 patients, none showed local progression at the site of SBRT, but 20 patients showed tumor growth at distant sites during follow-up. The 2- and 3-year overall survival rates were 45.1 and 36.1%, respectively. The 2- and 3-year progression-free survival rates were 35.4 and 26.5%, respectively. The interval between diagnosis and detection of OM (<2 vs. >2 years) and primary tumor site (esophagus vs. others) emerged as significant variables affecting survival. Grade 3 subacute and grade 4 chronic toxicities were observed in 1 and 2 patients, respectively. SBRT of 50 Gy in 10 fractions for OM from various primary tumors was shown to lead to good clinical outcomes from the viewpoints of local control and toxicity frequency. However, additional studies are required to identify the patient groups likely to receive maximal benefits from such treatment.

3D dosimetric verification of unity MR-linac treatments by portal dosimetry

Purpose and background3D dosimetric verification of online adaptive workflows is essential as their complexity is unprecedented in radiation oncology. The aim of this work is to demonstrate the feasibility of back-projection portal dosimetry for 3D dosimetric verification of Unity MR-linac treatments. Material and MethodsAn earlier presented 2D back-projection algorithm for the Unity MR-linac geometry was extended for 3D dose reconstruction and comparison against planned dose distributions. ‘In-air’ as well as in-vivo portal EPID images can be used as input. The method was validated using data from treatments of 5 patients (2 rectal, 2 prostate cancer and one oligo metastasis). 3D pre-treatment verification of the reference plan using ‘in-air’ EPID images was performed and compared against measured (with the Octavius 4D system) and planned (in the planning CT) dose distributions. In-vivo EPID dose distributions were compared to the TPS for the first three adaptations of all treatments. For all comparisons, dose difference values at the reference point and γ-parameters were reported. ResultsThe comparison against the OCTAVIUS 4D system (3%, 2 mm, local) showed y-mean = 0.52 ± 0.10 and y-passrate = 91.9%, 95% CI [85.4, 98.4], and ΔDRP = −0.1 ± 1.1%. Pre-treatment verification against TPS data (3%, 2 mm, global) showed y-mean = 0.52 ± 0.04, y-passrate = 93.5%, 95% CI [92.4, 94.6] and ΔDRP = −0.9 ± 1.5%. The averaged y-results for the in-vivo 3D verification were y-mean = 0.52 ± 0.05, y-passrate = 92.5%, 95% CI [90.2, 94.8] and ΔDRP = 0.8 ± 2.1%. Conclusion3D dosimetric verification of Unity MR-linac treatments using portal dosimetry is feasible, pre-treatment as well as in-vivo.