BOSTON—After the Boston Red Sox’s 86-year span without a World Series championship, perhaps the most familiar streak in Massachusetts is the half-century that a Kennedy has represented the state in the U.S. Senate.

Now, the news that Sen. Edward M. Kennedy has a cancerous brain tumor is forcing people to contemplate the day when he will no longer be there.

“It’s almost incalculable,” said Thaleia Schlesinger, whose brother, former Sen. Paul Tsongas, toiled in Kennedy’s oversize shadow before resigning in 1984 to cope with cancer that eventually killed him in 1997. “He’s the go-to guy over and over again. You just look at the universities, the hospitals, the high-tech industry, education, never mind health care. He’s always been there.”

Immigrants lining up at the John F. Kennedy Federal Building, tourists strolling on the Rose F. Kennedy Greenway and ordinary folks who received handwritten thank-you notes from the senator or a surprise distinguished visitor at a family wake pondered a future without Ted Kennedy.

“Forty-six years is a long time to be a senator. That’s got to count for something when it comes to delivering for the state,” said Ron Mills, who runs the shoeshine stand next to 122 Bowdoin St., the Beacon Hill address John F. Kennedy claimed when he served in the House and Senate and was elected president in 1960.

The 76-year-old Kennedy was diagnosed with a malignant glioma, an especially lethal type of brain tumor. Most such patients die within three years, sooner if they are older.

On Wednesday, Kennedy was released from Massachusetts General Hospital in Boston and returned to the family compound at Hyannis Port to await test results that will help determine his treatment, which is expected to include chemotherapy and radiation.

Kennedy gave a thumbs-up to well-wishers and kisses to relatives as he walked out of the hospital. A square bandage on the back of his head marked the spot where doctors performed a biopsy on the brain tumor.

Before he and his wife, Vicki, got into a dark Chevrolet Suburban, Kennedy kissed his daughter, Kara, and his niece Caroline Kennedy, and embraced his son Patrick, a congressman from Rhode Island.

On the road to the Kennedy compound on Cape Cod, neighbors placed signs welcoming the senator home. “We wish you well Ted, The Sullivan Family,” one read.