Radiation Therapy Before Repeat Wide Resection for Unplanned Surgery of Soft Tissue Sarcoma ("Oops" Operation) Results in Improved Disease-Free Survival.

Purpose: The main goal of treatment of soft-tissue sarcomas is achieving wide negative margins to improve local control and prevent recurrence. The role of radiation therapy (RT) is well established in sarcomas of the extremities; however, its role in unplanned surgery of soft-tissue sarcoma (when a mass presumed to be benign is resected and the pathology comes back as sarcoma, usually referred to as an "oops" operation) is inconclusive. This article reports on the effect of RT after an unplanned surgery before the reresection. Methods and Materials: A total of 65 patients who had undergone an unplanned resection of a postoperatively diagnosed soft-tissue sarcoma were treated with RT and/or surgery and retrospectively evaluated for disease progression. Treatment started with RT in 49 cases (75.4%), including 8 cases of no further surgery. A repeat wide resection was performed directly after the initial surgery in 16 patients, followed by RT in 15 of them. Results: The disease recurred in 7 out of 49 patients (14.3%) who received RT first and in 9 out of 16 (56.25%) who underwent reoperation before RT (P = .001). Disease-free progression was higher in cases of low-grade malignancy (P = .049). A clinical diagnosis of lipoma was associated with a better outcome than a diagnosis of nonlipoma (P = .034). The presence of residual tumor at reoperation did not affect disease control. Patient age, time between symptom onset and diagnosis, hospital level of initial diagnosis (tertiary versus nontertiary), anatomic site, tumor size, and margin status at the initial excisional biopsy were not significantly correlated with the outcome. Conclusion: Initiating treatment with RT followed by unplanned "oops" resection of soft-tissue sarcoma before the reresection improved disease-free survival as opposed to vice versa.

Extrapulmonary Small Cell Cancer: A New Insight into a Rare Disease.

INTRODUCTION: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. MATERIALS AND METHODS: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015-2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. RESULTS: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 <55%, while its role in limited disease was nonsignificant. DISCUSSION: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

The Theoretical Value of Whole-Lung Irradiation for COVID-19 Pneumonia: A Reasonable and Safe Solution until Targeted Treatments are Developed.

In this work, we considered the theoretical role of low-dose radiation therapy (approximately 0.5-1.0 Gy) in the treatment of respiratory distress syndrome associated with COVID-19 infection. Monte Carlo calculations were performed to gauge the ability to deliver low-dose radiation to the thoracic mid-plane using an orthovoltage machine. In addition, the potential harm of a single dose of 0.75 Gy (whole-lung irradiation) was assessed based on the recommendations of the BEIR-VII committee of the U.S. National Research Council. Based on the results of this work, it was determined that an orthovoltage machine (minimum 300 kVp) can be used to deliver 0.75 Gy dose to the lungs while respecting cutaneous tolerance. Using data from the BEIR-VII Committee, it is evident that the apparent benefits of such radiation treatment for patients suffering from severe manifestations of the COVID-19 infectious syndrome outweigh the potential loss of life due to radiation-induced malignancy. Although the vaccination against COVID-19 has become a reality, the spread and mortality in severely ill patients remain unacceptably high. The risk of outbreaks in the future is unknown. We suggest herein that low-dose radiotherapy at the bedside should be rigorously considered as a therapeutic option since it appears to be feasible and safe in the short and long term.

COVID-19 Vaccine-Induced Radiation Recall Phenomenon.

Radiation recall phenomenon (RRP) is an uncommon, late occurring, acute inflammatory skin reaction that emerges in localized areas coincident with previously irradiated radiation therapy (RT) treatment fields. RRP has been known to be triggered by a number of chemotherapy agents. To the best of our knowledge, this report is the first description of RRP after administration of the Pfizer-BioNTech vaccine for COVID-19, or any other currently available vaccine against COVID-19. Acute skin reactions were observed in 2 RT patients with differing timelines of RT and vaccinations. In both cases however, the RRP presented within days of the patient receiving the second dose of vaccine. For each RT course, the treatment planning dosimetry of the radiation fields was compared with the area of the observable RRP. RRP developed within the borders of treatment fields where prescription dose constraints were prioritized over skin sparing. Our observation is currently limited to 2 patients. The actual incidence of RRP in conjunction with Pfizer-BioNTech vaccine or any other vaccine against COVID-19 is unknown. For patients with cancer being treated with radiation with significant dose to skin, consideration should be given to the probability of RRP side effects from vaccinations against COVID-19.

Palliative Irradiation of Sacral Metastases: Must the Entire Bone Be Treated?

BACKGROUND AND PURPOSE: The sacrum as radiation target, raises a conceptual question: should the structure be regarded as a single unit or 5 distinct bones. If the entire sacrum must be irradiated there is a higher risk of rectal morbidity. MATERIALS AND METHODS: Images of 53 patients with sacral metastases were reviewed. The extent of sacral involvement was documented. The location of the rectum was recorded relative to the individual sacral bones. RESULTS: In 37.7% only S1 and S2 were involved by metastatic disease. In 41.5% there was metastatic involvement of S1-S3. In 1 patient there was involvement of S5 only. In 10 cases the entire sacrum was infested by metastatic disease. The rectum never extended to the height of S1. In 38% the upper pole of the rectum reached the S3 level. In toto, there were 64.2% where the inferior extension of sacral metastatic involvement did not overlap the upper pole of the rectum. Palliation of pain was achieved in 19/20 patients treated with partial sacral irradiation. CONCLUSIONS: The distal part of the sacrum is rarely involved in the metastatic process. Avoidance of radiation therapy to the lower sacrum simultaneously enables effective palliation and sparing of the adjacent rectum.

A critical assessment of the quality of radiation therapy in Israel: time to initiation of treatment of spinal cord compression as an index of efficiency.

INTRODUCTION: Radiotherapy departments function under workload pressure. We examined the process from referral to treatment initiation for spinal cord compression (SCC), one of the most daunting clinical scenarios in oncology. METHODS: We identified 235 patients with SCC, treated between 2013-2015. Two physicians classified cases as "emergent" or "urgent" (treatment within 24 or 72 h, respectively). RESULTS: The distribution of referrals over the week was uniform for inpatients. In contrast, there was a referral peak (62.27%) during the first two workdays for emergency ambulatory patients (p = 0.011). There were few weekend referrals in all groups (3.0%). There was a statistically shorter interval between referral and treatment for emergent versus urgent cases (0.94 days vs. 4.17 days; p < 0.0001, Bonferroni correction p < 0.0005). CONCLUSION: Time elapsed between referral and treatment of SCC may constitute a quality index in neuro-oncology. Modern departments of radiotherapy should determine the degree to which they can successfully implement such treatment. Patients with cancer and their physicians should be taught to recognize signs of SCC to expedite intervention.

Volumetric Modulated Arc Therapy as an Example of the Advanced Capability of Modern Radiotherapy.

BACKGROUND: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges. OBJECTIVES: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies. METHODS: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT. RESULTS: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases. CONCLUSIONS: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Single-institution Experience of SBRT for Lung Metastases in Sarcoma Patients.

OBJECTIVES: Lung metastasectomy is regarded as the standard procedure for improving the prognosis of patients with metastatic sarcoma. Few reports are available in the literature describing the value of stereotactic body radiation therapy (SBRT) of lung metastases from primary sarcoma as an alternative to surgical treatment. We therefore sought to expand the evidence base for this modality. MATERIALS AND METHODS: Twenty-two patients with metastatic sarcoma to lung were treated by SBRT. The retrospective analysis of overall survival, toxicity, and local control of 53 treated lesions is presented in the study. Lung lesions were grouped into 2 categories for follow-up: <10 mm or ≥10 mm diameter. RESULTS: Of 34 lesions <10 mm, 24 achieved complete response, 3 partial response, and 7 stable disease. The results of 18 lesions measuring >10 mm were as follows: 5 complete response, 5 progressive disease, and 8 stable disease. No progressive disease of all SBRT treated lesions was found at a median follow-up of 95 months (SD 32). Five-year overall survival of the entire group was 62% from the time of diagnosis and 50% from start of treatment. The treatment was well tolerated with minimal, mainly skin toxicity. CONCLUSION: SBRT is an effective tool that might be used as an alternative to operative treatment of lung metastases in sarcoma patients.

Primary high-grade soft-tissue sarcoma of the buttock: a rare but distinct clinical entity.

OBJECTIVE: Sarcoma arising in the region of the buttocks is a rare entity and therefore no consensus regarding management exists in the literature. METHODS: 16 patients diagnosed with localized, non-metastatic primary soft-tissue sarcoma (STS) in the buttock area, who were consecutively treated between 2005 and 2013, were retrospectively evaluated for the rate of local control, distant metastases and overall survival. RESULTS: Most tumours were classified as high grade (87.5%). The average time between the appearances of symptoms to diagnosis of sarcoma was 4.5 months. At the end of the observation period, 7 (44%) patients were alive without signs of progressive disease, 37.5% patients died as the disease progressed, 13 patients were free of disease and 3 (19%) patients were alive with signs of progressive disease. Seven (44%) patients developed local recurrence. Six (37.5%) patients developed distant metastases. The lung was the most common site of distant failure (four patients); other sites were the liver as well as the adrenal gland and kidney (one patient). Four patients had both distant and local progression, three patients experienced isolated local recurrence and two patients developed isolated distant metastases. 5-year local recurrence-free survival was 58% and 5-year distant metastases-free survival was 63%. CONCLUSION: It is unclear whether to subsume STS of the buttock under the rubric of pelvic tumours or tumours of the lower extremity. Either way, STS of the buttock seems to be characterized by local control, freedom from distant relapse and survival, which is inferior to accepted standards for either pelvic or lower extremity sarcomas. To improve this poor outcome, oncologists are encouraged to regard sarcoma of the buttock as a distinct clinical entity and to devise innovative therapeutic strategies accordingly. ADVANCES IN KNOWLEDGE: Sarcoma of the buttock area should possibly be regarded as a distinct entity.

Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy?

PURPOSE: To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR). METHODS: Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists. RESULTS: The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8 %). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9 ± 11.9 vs. 68.7 ± 10.8 years, respectively, p = 0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS). CONCLUSIONS: Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.

The impact of overall radiotherapy treatment time and delay in initiation of radiotherapy on local control and distant metastases in gastric cancer.

OBJECTIVES: To study the impact of time factors on local and distant metastases in stomach cancer. METHODS: 67 patients with gastric cancer who received adjuvant treatment were reviewed for the time to initiation of radiotherapy, overall duration of RT and the events of first local recurrence or distant metastasis. RESULTS: The risk probability of local recurrence is increased by 10% (HR=1.1, p=0.0009) in association with each additional day of radiotherapy and by 3.8% (HR=1.038, p=0.13) per increased day of waiting time before the initiation of RT. The risk probability of distant recurrence was associated with an increase of 7.4% (HR=1.074 p=0.0031) with each additional day of RT time and by 2.3% (HR=1.023, p=0.0598) following the increase of a day of waiting time. Each day of prolongation of RT beyond 36 days was associated with an increased risk of local recurrence by 10% (OR=1.1, p=0.015). Prolongation of waiting time prior to initiation of irradiation retained significance in multivariate analysis. CONCLUSION: There is an association between total treatment time and, to some extent, the time between the surgery and the initiation of radiation on local control and distant metastases.

The advantage of 3D conformal treatment of lumbar spine metastases in comparison to traditional PA or AP-PA techniques: restoring an intermediate niche of therapeutic sophistication.

BACKGROUND: To evaluate the effect of the 3D radiation field design on normal tissues compared with commonly used appositional fields in patients with lumbar spine metastases. METHODS AND MATERIALS: Ten comparative treatment plans for radiation of lumbar spine metastases were compared for posterior and anterior- posterior fields with 3D plans. RESULTS: The PTV coverage in all comparative plans was similar. V 15 of the bowel in 3D, AP-PA and PA plans was 6.7 Gy (SD 6.47), 39.8 Gy (SD 11.4) and 37.3 Gy (SD15.7), respectively (p < 0.0001). The mean dose to both kidneys was 9.6 Gy (SD 4.8), 4.1 Gy (SD 3.9) and 4.6 Gy (SD 4.4) for appropriate plans (p = 0.002). Maximal dose to the spinal cord was 30.6 Gy (SD 2.1), 33.1 Gy (SD 9.8) and 37.7 Gy (SD 2) for 3D, AP-PA and PA plans. CONCLUSION: 3D conformal treatment planning of lumbar vertebral metastases was significantly better in term of bowel and spinal cord exposure compared to AP-PA and PA techniques. The exposure of the kidneys in 3D plans, while greater than in the comparative plans, did not violate accepted dose-volume thresholds.

AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors.

Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors.

Improved treatment of the breast and supraclavicular fossa based on a simple geometrical principle.

In breast cancer, nodal irradiation has become routine, but adds time and creates concerns for field overlap if the "match" is not accurate. We developed a technique to address these issues by using only one isocenter for both areas. Tangents are designed at simulation. The isocenter is then shifted to the upper border of the breast using a straightforward geometrical calculation. After determining the new isocenter, fields are recreated wherein the tangents are treated with a quarter beam and the supraclavicular field fashioned with a half-beam block. The gantry, collimator, and couch angles of the supraclavicular field are adjusted to achieve an accurate match. Ten patients were evaluated. Doses to the spinal cord and brachial plexus were lowered relative to conventional techniques. The hot spots were not augmented. In comparison with standard arrangements, setup time decreased. Accurate matching was consistently achieved and verified by portal imaging. A new approach for treating the supraclavicular fossa is easily executed. Advantages include negligible doses to the critical neural structures (i.e., spinal cord and brachial plexus), optimized matchline, and reduced setup time.

Radiation therapy for palliation of sarcoma metastases: a unique and uniform hypofractionation experience.

Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma.

Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer.

PURPOSE: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. METHODS AND MATERIALS: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 degrees , 53 degrees , 107 degrees , 158 degrees , 204 degrees , 255 degrees , and 306 degrees . Beam arrangement 2 consisted of gantry angles of 30 degrees , 90 degrees , 315 degrees , and 345 degrees ; a gantry angle of 320 degrees /couch, 30 degrees ; and a gantry angle of 35 degrees /couch, 312 degrees . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. RESULTS: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. CONCLUSIONS: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

Three-dimensional non-coplanar conformal radiotherapy yields better results than traditional beam arrangements for adjuvant treatment of gastric cancer.

PURPOSE: The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. METHODS AND MATERIALS: A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field "box" was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. RESULTS: The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. CONCLUSION: Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical practice.

A single-team experience of limb sparing approach in adults with high-grade malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) is the most common subtype of soft-tissue sarcoma (STS). When located in a limb, MFH, is currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). During 8 years, 42 adult patients with high-grade limb MFH were approached by LSS and RT. Our results reflect a single-team experience and point to several important conclusions. High grade MFH, treated by conservative approach, lead to a 10-year relapse-free survival of 62% and a 10-year overall survival rate of 80%. Recurrences of MFH tend to occur during the first 2 years. Relapse-free survival was affected mainly by location in the lower limb vs. the upper limb, irrespective of the tumor size. Patients who had their diagnostic biopsies in another medical center had a greater tendency to local and systemic relapse. It seems that the most important clues for disease-free survival are the team experience and cooperation. All other factors are tumor-biology dependent, and thus far are beyond our control.